Obesity in Pregnancy
The purpose of this document is to review the risks of obesity in pregnancy and pertinent management issues for clinicians caring for these women. In addition, important areas for future research aimed at improving the understanding of obesity in pregnancy and potential strategies to improve outcomes will be highlighted.
Obesity is now epidemic in many developed countries secondary to decreased physical activity combined with an abundance of cheap, high-caloric foods. In the United States, 33% of women aged 20 years or older are obese (body mass index ≥30 kg/m2) (1). The problem is greatest among non-Hispanic black women (53.9%) and Mexican-American women (42.3%) as compared to non-Hispanic white women (30.2%) (1). An analysis of 2004-2005 data from the Pregnancy Risk Assessment Monitoring System (PRAMS) found that approximately one in five U.S. women who delivered were obese and that this prevalence was even higher among black women and women with public insurance (2). Maternal obesity increases the risk of multiple adverse pregnancy outcomes including congenital anomalies (3), miscarriage (4), preeclampsia (5)(6)(7), gestational diabetes (GDM) (6)(7), fetal macrosomia (6)(7), and stillbirth (5)(7). Obesity also is associated with multiple labor abnormalities, including an increased risk of induction of labor (7)(8), post-dates pregnancy (9)(10), prolonged labor (11), labor augmentation with oxytocin (11)(12), excessive blood loss at delivery (7)(13), and cesarean delivery (5)(6)(7)(14). Obese women who are delivered by cesarean are at greater risk of complications such as longer operative times, excessive blood loss, wound infections, and post-operative endometritis (15). Not only are large numbers of women overweight or obese prior to pregnancy, but many women gain an excessive amount of weight during pregnancy (16), thus compounding their obstetrical risks and making them more likely to retain weight postpartum (17). Maternal obesity can also adversely impact the health of offspring, including increasing the risk of neonatal death (18) and childhood obesity (particularly in the setting of excessive gestational weight gain [GWG)]) (19).
The most commonly used measurement for defining obesity is body mass index (BMI), which refers to an individual's weight in kilograms divided by the square of her height in meters. The National Institutes of Health (NIH) and the World Health Organization (WHO) define underweight as a BMI <18.5 kg/m2, normal weight as a BMI 18.5-24.9, overweight as a BMI 25.0-29.9, and obesity as a BMI ≥30. Obesity is further defined as class I: BMI 30-34.9, class II: BMI 35-39.9, and class III: BMI ≥40. One limitation of using BMI is that some athletes, for example, will have higher body weights and thus increased BMI's due to increased muscle mass rather than fat mass. However, in part because BMI is so easily calculated, it is the most commonly used measure in research and health policy.
Gestational Weight Gain
Weight gain in pregnancy is generally considered to be the difference between a woman's weight at the last prenatal visit and her pre-pregnancy weight or her weight at her first prenatal visit. Pre-pregnancy BMI should be documented on the prenatal chart to serve as a reminder to the clinician of the increased risks of obesity in pregnancy and the need to counsel the woman on appropriate GWG. Excessive GWG, even among normal weight women, is associated with adverse pregnancy outcomes such as hypertensive disorders, large for gestational age (LGA) infants, and cesarean section (20)(21)(22) and adverse neonatal outcomes such as meconium aspiration, seizures, assisted ventilation, and hypoglycemia (23). In 2009, the Institutes of Medicine (IOM) released revised recommendations for appropriate gestational weight gain (GWG) which are dependent upon a woman's pre-pregnancy BMI:
To calculate BMI go to www.nhlbisupport.com/bmi; calculations assume a 0.5-2 kg (1.1-4.4 lbs) weight gain in the first trimester.
Indeed, studies suggest that obese women can decrease their risk for adverse outcomes by having low GWG (20)(22)(24). Unfortunately, in a recent study of nearly 53,000 U.S. women, approximately 40% and 60% of normal-weight and overweight women, respectively, had GWG exceeding IOM recommendations (16).
The immediate obstetric and neonatal complications resulting from excessive GWG are of great concern, but the potential long-term effects on the health of both the mother and her offspring are also being elucidated. Increasing parity, independent of socioeconomic status, is associated with obesity later in life (25). This effect may be compounded by excessive GWG during the individual pregnancies, which is a significant risk factor for post-partum weight retention (17)(24)(26). Studies have also found that excessive GWG, particularly among obese women, is associated with obesity in children (19)(27). Weight retention increases the risks in subsequent pregnancies. In an analysis of 151,025 linked pregnancies in Sweden, women whose BMI's increased by three or more units during an average of two years between pregnancies were at greater risk of hypertensive disorders, GDM, cesarean delivery, stillbirth, and large-for-gestational age infants in their second pregnancies than women whose BMI's changed little (28). The inter-pregnancy interval may thus prove to be a particularly important time to target interventions aimed at achieving weight reduction. Clinicians should specifically counsel women (particularly those who are obese and/or had excessive GWG) at their postpartum visits regarding weight loss to improve their future reproductive outcomes as well as their long-term health.
The American College of Obstetrics and Gynecology (ACOG) states that, in the absence of medical or obstetrical complications, pregnant women can adhere to the Centers for Disease Control (CDC) recommendations for 30 minutes or more of moderate exercise on most days of the week. Exercise may even play a role in the primary prevention of GDM, particularly among obese women (29). Identifying effective and safe means of achieving appropriate weight gain in pregnancy is a critical area for future investigation.
Risks of Obesity in Early Gestation
Obese women appear to be at increased risk of miscarriage. In a recent meta-analysis, a BMI ≥25 was found to be associated with miscarriage regardless of mode of conception (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.25-2.25) (4). There is evidence that obese women have greater rates of miscarriage after assisted reproductive techniques including oocyte donation and ovulation induction (4). Given that obesity is associated with the polycystic ovarian syndrome (PCOS) and infertility related to ovulatory dysfunction, many obese women seek assisted reproductive technologies. Women who seek infertility treatment are often older which may further compound the obstetrical risks associated with obesity. Clinicians should counsel obese women on the benefits of weight loss prior to beginning infertility treatment and on the risks of obesity in pregnancy.
Maternal obesity is a risk factor for several types of congenital anomalies including neural tube defects (NTDs), cardiovascular anomalies, and cleft lip/palate (3)(30)(31). The association between obesity and NTDs (3)(30)(31)(32)(33)(34)(35) in the U.S. has persisted even after the initiation of folic acid fortification to enriched grain products in the 1990s (36). The underlying reason for this association is not known. Obesity appears to be a risk factor for NTDs independent of folic acid intake in supplements or diet (32,33,35). However, a high BMI is inversely associated with folate intake in supplements or diet (37)(38)(39). In a study which controlled for folate intake, a higher BMI in women of child-bearing age was associated with a lower serum folate level (40), leading the author to speculate that obese women may require more folic acid supplementation than women of normal weight.
Maternal obesity poses a challenge for ultrasonographic detection of fetal anomalies. In a recent retrospective cohort study, increasing maternal BMI was associated with decreased detection of anomalous fetuses by both second trimester standard and targeted ultrasound examinations (41). This translated to a 20% difference in anomaly detection rates in obese women compared to normal-weight women. Evaluation of the fetal heart can be particularly challenging in obese women. This is especially concerning in women with pre-existing diabetes with poor glycemic control, a significant risk factor for cardiac anomalies.
Risks of Obesity in Late Gestation
Gestational Diabetes and Preeclampsia
Just as obesity in the non-pregnant state is associated with type 2 diabetes and hypertension, pre-pregnancy obesity is a significant risk factor for the development of GDM and preeclampsia (5)(6)(7). In a study of just over 16,000 women, obesity and morbid obesity were associated with odds ratios of 2.6 and 4.0, respectively, for GDM and 1.6 and 3.3, respectively, for preeclampsia (6). Furthermore, excessive GWG is associated with an increased risk for preeclampsia and large-for-gestational age infants (22).
GDM is the clinical manifestation of glucose intolerance in pregnancy. Normal pregnancy is associated with decreased insulin sensitivity. For obese women, who are often already more insulin-resistant than normal-weight women, pregnancy will often tip them into overt hyperglycemia. It's important to remember that some obese women, particularly those who have had limited routine medical care prior to pregnancy, may actually have undiagnosed type 2 diabetes. Consideration should be given to initiating home blood glucose monitoring (fasting and postprandial) early in pregnancy, especially for obese women with a prior pregnancy affected by GDM. Women who do develop GDM are at increased risk of developing type 2 diabetes later in life (42). It is important for them to be screened postpartum for diabetes. Although this can be done using a fasting glucose, a two hour 75 gm glucose tolerance test can provide information with regards to impaired glucose tolerance in the absence of frank diabetes.
The underlying mechanism by which obesity increases the risk of preeclampsia is unknown but may involve subclinical inflammation, which plays a role in the development of cardiovascular disease in non-pregnant obese women. Given the increased risk for cardiovascular disease among obese women, strong consideration (particularly in women with pre-existing hypertension) should be given to obtaining a baseline electrocardiogram or, dependent on history and exam findings, an echocardiogram. A baseline quantification of 24 hour urine protein can also be useful in distinguishing between hypertensive-associated renal disease and the development of superimposed preeclampsia later in pregnancy.
Some obese women may have obstructive sleep apnea and, although data are limited, this condition may be associated with impaired fetal growth (43) and can pose a particular problem for women post-operatively. For women whom the clinician suspects may have sleep apnea, pregnancy may be an ideal time for further evaluation.
Intrauterine Fetal Demise
Maternal obesity is a significant risk factor for stillbirth, particularly late stillbirth (5)(44). Among over 54,000 women in the Danish National Birth Cohort, a BMI ≥30 was associated with a hazard ratio for fetal death at 37-39 weeks of 3.5 and at 40+ weeks of 4.6 when compared to normal-weight women (45). The mechanism by which obesity increases the risk of stillbirth is unknown, as the risk persists even after adjusting for confounding factors such as diabetes and preeclampsia (45). Placental dysfunction may be an important contributor (45), but further research in this area is needed.
Risks of Obesity in the Peripartum Period
Maternal obesity is associated with multiple labor abnormalities. Obese women have increased rates of cesarean delivery when compared to normal weight women (5)(6)(7)(14). This is in large part due to labor abnormalities such as "failure to progress" and/or "cephalopelvic disproportion" (46), and persists even after adjustment for infant birth weight (13)(14)(46). Progression in the first stage of labor is particularly slow for obese women as compared to normal weight women (11)(13). Several theories have been proposed to explain this increased rate of cesarean delivery, including increased fat deposits in the pelvis, decreased maternal expulsive efforts, and impaired uterine contractility. The majority of evidence suggests that myometrial contractility is impaired in the setting of obesity. In vitro studies indicate that myometrial strips from obese women contract with less frequency and amplitude than those from normal weight women (13). Furthermore, leptin (a product of adipose tissue) (47) and cholesterol (48) both inhibit the contractility of myometrial strips. Clinically, obese women are at decreased risk of spontaneous preterm birth (SPTB) (but increased risk of indicated preterm birth) (49)(50) and may have fewer preterm contractions (49).
When considering a woman's likelihood of success during a trial of labor after a prior cesarean delivery, obesity is a particularly important factor. In a study from the NIH Maternal-Fetal Medicine Units Network, after one prior cesarean delivery, obese women had a trial of labor success rate of 68% vs. 79.6% for non-obese women (51). When combined with induction of labor and no prior vaginal delivery, the success rate for obese women was less than 50%.
Obese women also have higher rates of emergency cesarean delivery for non-reassuring fetal status (52). They should be counseled that it may be more difficult to adequately externally monitor the fetal heart rate and contraction pattern and that an emergent cesarean delivery, if needed, may be more difficult than in normal weight women.
Not only is obesity a consistent risk factor for cesarean delivery, but it also increases the risk of surgical complications including wound infection, longer operative times, endometritis, and excessive blood loss (15). Although subcutaneous drains have not consistently been shown to decrease morbidity after cesarean section, a meta-analysis found that suturing the subcutaneous layer if it is thicker than 2 cm is associated with decreased rates of wound disruption (53). This should be considered for all obese women. More research is needed to determine if, among women with a large panniculus, it is preferable to locate the skin incision superior to the panniculus.
Administration of anesthesia can be particularly challenging in obese women. There is an increased risk of epidural/spinal placement requiring multiple attempts and an increased risk of difficult intubation if general anesthesia is required (52). Obese women also have increased rates of sleep apnea (54). Consideration should be given to obtaining an anesthesia consultation antenatally.
Pregnancy, cesarean delivery, and obesity all increase the risk for thromboembolism. It has been suggested that obese women (without a prior history of thromboembolism) undergoing cesarean delivery have sequential compression stockings placed and be encouraged in early ambulation. If other risk factors are present such as age >35 years, preeclampsia, and emergency cesarean it may be beneficial to administer low molecular weight heparin (55). However, it's important to remember that no adequately powered, randomized, controlled studies of thromboprophylaxis after cesarean section have been performed and the optimal duration of thromboprophylaxis after surgery is unknown.
The incidence of bariatric surgeries in the U.S. increased by 800% between 1998 and 2005, with 83% of surgeries in the 18-45 year old age group occurring in women (56). Commonly performed procedures are the Roux-en-Y gastric bypass (restrictive and malabsorptive) and adjustable gastric banding (restrictive). Reproductive-aged women undergoing bariatric surgery should have counseling regarding contraception and future pregnancy planning prior to the procedure. The authors of a recent systematic review state that while there is insufficient evidence regarding contraceptive efficacy after bariatric surgery, concerns exist regarding potentially impaired absorption of oral contraceptive pills (56). Furthermore, existing data suggest that bariatric surgery may have a beneficial effect on fertility with correction of the abnormal hormonal profiles seen in PCOS and increased regularity of menses (56). Rapid weight loss occurs after bariatric surgery and it has generally been recommended that women wait 1-2 years after surgery before conceiving (57). Bariatric surgery appears to decrease the incidence of hypertensive diseases in pregnancy, pre-pregnancy diabetes, and gestational diabetes (56)(58)(59). Neonatal outcomes after bariatric surgery do not appear to be worse and may, in fact, be better (56). The incidence of macrosomia is decreased in women after bariatric surgery (56)(59)(60).
Attention should be paid to potential nutritional abnormalities among women who have had bariatric surgery. The most common deficiencies are in protein, iron, vitamin B12, folate, vitamin D, and calcium. Consideration should be given to screening for these deficiencies before or in early pregnancy and, especially if supplementation is required, intermittently during the antenatal period.
"Active band management," or removing fluid from the adjustable gastric band to allow increased intake and even to relieve nausea and vomiting in early pregnancy has been described (61)(62). Consultation in these cases should be made with a bariatric surgeon. In women who have undergone bariatric surgery and have gastrointestinal complaints during pregnancy, a surgery-related complication (such as bowel obstruction, anastamotic leak, hernia, or gastric band migration) should be considered and investigated.
Women who have had a malabsorptive procedure are at risk for dumping syndrome, where the stomach rapidly empties sugars and carbohydrates into the small intestine. This can result in fluid accumulation in the small intestine with symptoms of nausea, vomiting, diarrhea, and abdominal cramps. It can also cause hyperinsulinemia with subsequent hypoglycemia. Alternative screening techniques (such as home glucose monitoring) for GDM may be needed in women with dumping syndrome because they may not tolerate a 50 gm glucose load. Women who have had a malabsorptive procedure may have altered medication absorption and immediate release formulations are preferred over extended release. If it is critical to achieve appropriate serum drug levels, monitoring may be needed.
Bariatric surgery in and of itself is not an indication for cesarean delivery. However, many of these women are still obese and thus at increased risk for labor abnormalities related to obesity. If a woman has had many prior abdominal surgeries, it may be prudent to consult with a bariatric surgeon prior to labor.
The increasing rate of obesity in many populations around the world is one of the most significant healthcare challenges of modern times. There is little encouraging evidence that this trend is likely to change in the near future. Although great advances have been made in obstetrical care over the last several hundred years, this field is not immune from the complications of obesity. Not only are obese women at much greater risk of pregnancy complications than normal weight women, but it appears that the fetuses of obese women may be programmed for future health complications as well. It is imperative that modern obstetricians understand the implications of obesity in pregnancy and be prepared to appropriately care for these women. It is equally important that research efforts be targeted not only at understanding the epidemiology but also the biology of obesity in pregnancy. It is through this type of investigation that strides can be made in improving the pregnancy outcomes of obese women.