Journal of Perinatology (2014) 34, 495–502 & 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp

STATE-OF-THE-ART Super in : difficulties in clinical management

A Martin, I Krishna, J Ellis, R Paccione and M Badell

As the obesity pandemic continues in the United States, obesity in pregnancy has become an area of interest. Many studies focus on women with body mass index (BMI) X30 kg m À 2. Unfortunately, the prevalence of patients with BMI X50 kg m À 2 is rapidly increasing, and there are few studies specifically looking at pregnant women in this extreme category. The purpose of this article is to highlight some of the challenges faced and review the literature available to help guide obstetricians who might encounter such patients.

Journal of Perinatology (2014) 34, 495–502; doi:10.1038/jp.2014.4; published online 6 February 2014 Keywords: complications; morbid obesity; obesity; pregnancy; super obesity

INTRODUCTION on the complex interaction between genetic background and In 2009 to 2010, more than one-third of adults in the United States environmental factors. Genetic background explains only an 9 were obese (body mass index (BMI) X30 kg m À 2).1 Perhaps, a estimated 40% of the variance in body mass. Genetic more startling statistic is the increasing prevalence of morbid heritability plays a significant role in obesity with the risk of and super obesity (BMI X40 and X50 kg m À 2, respectively). In a childhood obesity significantly increased if one parent is obese 10 report looking at these groups in the United States between 2000 and even higher if both parents are affected. Obesity is likely to and 2005, the prevalence of self-reported BMI over 50 kg m À 2 result from the interaction of many different gene–gene and increased by 75%.2 The heaviest BMI groups have been increasing gene–environment interactions. The use of the genome-wide at the fastest rates for 20 years; consequently, the obstetrician will association approach has identified many genes with robust be caring for more super obese women. Obesity has long been associations but usually with only modest contributions to overall 11 perceived as a risk factor for poor pregnancy outcomes,3–5 but genetic susceptibility to obesity. In contrast, a small number of data on super obesity are limited. We recently cared for 34-year- single-gene mutations have been identified that clearly cause old G1P0 with a prepregnancy weight of 630 lb (BMI obesity in rare patients. Environmental factors such as diet and 98.67 kg m À 2). The purpose of this article is to highlight some of exercise play an important role in the development of obesity. The the challenges faced and review the literature available to help significant increase in obesity since the 1980s is largely secondary guide obstetricians who might encounter similar patients. to alterations in environmental factors that increase energy intake and reduce physical activity. Reasons for this include more meals are eaten outside the home, there is greater availability of fast Definition of obesity food and snack foods, serving sizes are larger and daily physical The World Health Organization (WHO) defines obesity as a BMI of activity has decreased because of sedentary lifestyles. X30 kg m À 2.6 Obesity is subdivided into three classes: class 1 Obesity is commonly associated with alterations in metabolic includes those with a BMI of 30 to 34.9 kg m À 2, class 2 includes function, specifically , , dyslipidemia and BMI of 35 to 39.9 kg m À 2 and class 3 includes those with a BMI of increased blood pressure. Obesity is also associated with a long list X40 kg m À 2.7 In the surgical literature, class 3 obesity is often of pregnancy complications. In general, the higher the patient’s further divided into morbid obesity for BMI of 40 to 49.9 kg m À 2 BMI, the higher the chance of complication. This ‘dose-response’ and super obesity for BMI 450 kg m À 2 (Table 1).4 Although has been well demonstrated for pre-eclampsia with the risk commonly seen and used throughout medical literature, these doubling with each 5 to 7 kg m À 2 increase in prepregnancy BMI;12 definitions are not standardized, and authors have used varying in addition, for each 1 unit increase in pregravid BMI, the BMI values to define the same term. Furthermore, there are no risk of cesarean delivery increases by B7%.13 Given this, patients terms in the literature to address patients such as the one we should be counseled to attempt to be as close to ideal body encountered with a BMI approaching 100 kg m À 2. weight before pregnancy and practitioners should have higher index of suspicion for pregnancy complications the higher the patient’s BMI. Pathophysiology of obesity Obesity is usually caused by an excessive intake of calories in relation to energy expenditure over a significant period of time. Developmental origins of health and disease Increases in body results from even minor, but chronic, There is growing evidence linking maternal prepregnancy BMI and differences between energy intake and energy expenditure. In gestational weight gain to offspring adiposity throughout life, 1 year, the ingestion of only 5% more calories than expended can from infancy through adolescence and to adulthood.14,15 It has promote the gain of B10 lb in adipose tissue.8 Weight depends been suggested that the obesogenic environment experienced

Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA. Correspondence: Dr A Martin, Department of Gynecology and Obstetrics, Emory University, 69 Jesse Hill Jr. Drive, SE, 4th Floor, Glenn Building, Atlanta, GA 30303, USA. E-mail: [email protected] Received 7 August 2013; revised 23 December 2013; accepted 7 January 2014; published online 6 February 2014 Super obesity in pregnancy A Martin et al 496 dating and viability (see Figure 1). In addition to routine prenatal Table 1. Obesity definitions labs, super obese women should have a complete blood count, Term Definition chemistry, liver function test, electrocardiography and 24 h urine protein ordered at their initial visit. An early rapid screen Obesity BMI 430–39 kg m À 2 should be performed and repeated between 24 and 28 weeks if Class 1 obesity* BMI X30–34.9 kg m À 2 normal. In addition, as Gunatilake et al.7 suggested, women with Class 2 obesity* BMI X35–39.9 kg m À 2 BMI X40 kg m À 2 may benefit from an echocardiogram to Class 3 obesity* BMI X40 kg m À 2 7 À 2 evaluate for underlying, undiagnosed cardiomyopathy. In the Morbid obesity BMI X40–49 kg m second trimester, super obese women should be counseled on X À 2 Super obesity BMI 50 kg m maternal and fetal risks and limitations of ultrasound, and Abbreviation: BMI, body mass index. appropriate consultations should be considered (see Figure 2). *World Health Organization definition. Maternal risks Obese women are at an increased risk of prepregnancy medical before and during conception and early pregnancy may induce 16,17 illnesses such as , diabetes, gallbladder disease, methylation differences, causing changes in gene expression, asthma and obstructive sleep apnea that have been associated tissue structure and organ development. These changes may with a twofold risk of stroke and underlying cardiac dysfunction.25 result in subsequent cardiometabolic health consequences in the 18 If underlying cardiopulmonary disease is suspected, the patient adult offspring. Given this possible developmental origin of may benefit from a cardiology or pulmonology referral for obesity, preconception should be emphasized and additional testing such as an echocardiogram, sleep study or strongly encouraged. pulmonary function testing. Obesity and pregnancy are independent risk factors for venous Preconception weight loss thromboembolism (VTE), and VTE is one of the leading causes of 26,27 The American College of Obstetricians and Gynecologists maternal death in the United States. The risk of VTE appears to encourages preconception counseling for the obese patient, increase with increasing levels of obesity. A retrospective cohort including education about the maternal and fetal risks of obesity study of over 142 000 found women weighing 90 to in pregnancy, and encouragement to participate in a weight 120 kg had a twofold increased risk of antepartum VTE as compared with women weighing o90 kg, and women weighing 4120 kg had reduction programs including diet, exercise and behavior modifica- 28 tion before conception.5 There are limited data addressing more than a threefold increased risk. Immobility in addition to preconception counseling and weight loss; however, recent obesity has been shown to significantly increase the risk of VTE among pregnant women.27,29 and obese women studies in the primary care setting reassure us that preconception À 2 weight loss is achievable. The Louisiana Obese Subjects Study (BMI 425 kg m ) with a history of immobilization have an (LOSS) showed that when primary care physicians were trained to adjusted OR of 62.3 (95% confidence interval (CI) 11.5 to 337.6) for implement structured diets, group counseling and pharmaco- antenatal VTE and 40.1 (95% CI 8.0 to 201.5) for postnatal VTE as compared with women with a BMI of o25 kg m À 2 and no therapy to treat patients with extreme obesity (BMI 40 to 29 60 kg m À 2), over 30% achieved X5% weight loss over 24 immobilization. From these data, one can deduce that the months.19 Results of the practice-based opportunities for weight risk of VTE among the super obese is confounded by immobility reduction (POWER) study at the University of Pennsylvania indicate due to their weight. There are no randomized control trials or that primary care practitioners, working with medical assistants, can professional guidelines to assist with the decision to start provide effective weight management in patients with BMI of 30 to prophylactic anticoagulation among these women during the 50 kg m À 2. Quarterly provider visits and medical assistant antepartum or postpartum period. After a careful discussion of counseling, along with meal replacements and medications, was the risks and benefits, anticoagulation should be strongly effective in inducing X5% weight loss in 35% of the participants.20 considered and individualized. The risk of hypertensive disorders in pregnancy among obese In the Hopkins POWER study, patients were randomized 3,28 to behavioral weight loss interventions delivered remotely women is increased, and the risk appears to have a linear relationship with BMI. In one prospective study of 416 000 (by telephone) or in-person combined with a web-based weight À 2 loss tool. Initial behavioral interventions took place weekly pregnant patients in the United States, a BMI of 30 to 34.9 kg m for both groups. Weight decreased by X5% over 24 months in was associated with a 2.5 times increased risk of gestational hypertension as compared with ideal-weight controls, and a BMI 38 and 41% of patients in the remote and in-person interventions, À 2 3 respectively.21 In a slightly less time-intensive and less costly of X35 kg m was associated with a 3.2 times increased risk. We can only extrapolate what the risk might be among those with a approach, 20% of the participants in the POWER study conducted À 2 at Harvard achieved X5% weight loss with brief telephone BMI of X50 kg m . Similarly, the risk of contacts that initially occurred every month in combination with increases with rising maternal BMI, with obese women having a a web-based weight loss program.22 These LOSS and three 2.6 times increased risk compared with ideal-weight controls and morbidly obese women having a fourfold increase in gestational POWER studies indicate that weight loss is not only achievable 3 in the primary care setting before pregnancy, but there are diabetes. several different and complimentary ways to accomplish weight The risk of macrosomia has also been shown to increase with loss goals. increasing BMI. In a large retrospective cohort study including 464 000 births, super obese women were significantly more likely to have macrosomic infants than their obese counterparts 4 PRENATAL CARE (adjusted relative risk (RR) of 1.8). In addition, they should also be counseled on their risk of cesarean section that approaches Often obese women have irregular periods or have suffered from 50% for the morbid and super obese.3,4 infertility and might not recognize signs of pregnancy until later than their ideal-weight counterparts.23 Several retrospective studies and a recent systematic review found that obese women Fetal risks are at increased risk of (odds ratio (OR) 1.3).24 Ideally, The morbid and super obese pregnant woman should be an ultrasound should be performed as early as possible to confirm counseled on their risk of fetal anomaly, particularly neural tube

Journal of Perinatology (2014), 495 – 502 & 2014 Nature America, Inc. Super obesity in pregnancy A Martin et al 497

Positive pregnancy test and BMI ≥ 40-50 kg/m2

Dating and viability ultrasound

First Trimester*

Consults Ultrasound Labs

Offer first trimester Early glucose Maternal Cardiology Routine (if symptoms of screening screening, Fetal underlying between 11 Liver function Medicine and 13 weeks labs tests, cardiac disease) Creatinine, 24 hour urine protein Counseling on Baseline EKG, maternal and consider maternal fetal risks echocardiogram

Figure 1. Prenatal care. BMI, body mass index; EKG, electrocardiography. *If second trimester, see Figure 2.

Second Trimester

Ultrasound Labs Hospital Planning

Rapid Detailed Serial growth Consider glucose L&D and OR Anesthesia Pharmacy Social Work anatomy + after 24 antenatal testing screen^ equipment* Consult Consult Consult fetal echo weeks after 32 weeks

Dosing of Transportation thromboprophylaxis planning to and & antibiotics from the hospital

Figure 2. Prenatal care. ^ Do not perform if the patient is a pregestational diabetic or if she is diagnosed with gestational diabetes after an early screen. * See Tables 3 and 4. Perform the rapid glucose screen between 24 and 28 weeks if an early screening test was negative or not performed. L&D, labor and delivery; OR, operating room. defects (NTDs). In a retrospective study including 292 open NTDs estimated dietary folate intake, and there appeared to be no among 420 362 women, the adjusted OR for NTD was 1.2 per protective effect against NTD with recommended folate intake in 10-kg incremental rise in maternal weight.30 In another series obese women.31 Other birth defects associated with maternal including 604 newborns, the relative risk of NTD was 3 to 4 for obesity include craniofacial abnormalities and heart defects.32,33 women weighing 4100 kg.31 The effect was independent of The above studies are limited when considering risk among

& 2014 Nature America, Inc. Journal of Perinatology (2014), 495 – 502 Super obesity in pregnancy A Martin et al 498 fetuses of the morbid and super obese as most of them included recommended total weight gain for obese women with BMI of women with BMI of X30 or X40 kg m À 2 but did not quantify X30 kg m À 2 is 11–20 lb (5 to 9 kg). Recent studies have suggested those with BMI X50 kg m À 2. that women who are in the morbid and super obese categories Offspring to obese mothers are more likely to have low Apgar who gain weight below the IOM guidelines may have improved scores, and the risk of admission to the neonatal intensive care maternal and fetal outcome.45–47 units is increased 3.5-fold.33,34 Maternal obesity is associated with Hinkle et al.45 evaluated weight gain during pregnancy and fetal a more than doubled risk of and neonatal death as growth among 122 327 obese pregnant women with a compared with women of ideal weight.33,35,36 Again, further prepregnancy BMI of X30 kg m À 2. Findings suggested weight research is needed to determine whether these risks are gains that ranged from a loss of 4.9 kg to a gain of 4.9 kg among substantiated and exaggerated in the fetuses of the super obese. class II obese women (BMI 35 to 39.9 kg m À 2), and class III (BMI X40 kg m À 2) obese women did not significantly increase the Ultrasound and prenatal diagnosis odds of a small–for-gestational age and had the benefit of decreasing macrosomia. A population cohort study by Blomberg46 Fetuses of obese women are at an increased risk for fetal noted that obese women (class III) who lost weight during anomalies compared with fetuses of normal-weight parturients, pregnancy had a decreased risk of cesarean delivery (OR 0.77, 95% with the anomalies often involving the fetal cardiac or central CI 0.60 to 0.99), large-for-gestational-age births (OR 0.64, 95% CI nervous systems as described above. Targeted ultrasound by a 0.46 to 0.90) and no significantly increased risk for pre-eclampsia, maternal–fetal medicine specialist should be considered between excessive bleeding during delivery, instrumental delivery, low 18 and 22 weeks. Further compounding the risk of fetal anomaly is Apgar score or fetal distress compared with obese (class III) the decreased sensitivity of antenatal ultrasound among women women gaining within the IOM recommendations. In this study, with high BMI because of the depth of insonation required and however, there was an increased risk for small for gestational age the absorption of ultrasound energy (dropout) by the abdominal (OR 2.34, 95% CI 1.15 to 4.76) among women in obesity class III adipose tissue.37,38 Best et al.38 found that the odds of congenital losing weight.46 These studies suggest that weight gain below the anomaly detection were significantly decreased in obese women IOM guidelines may improve outcomes, but there is insufficient (adjusted OR, 0.77; 95% CI 0.60 to 0.99; P ¼ 0.046). To overcome evidence to recommend weight loss for the super obese gravida. these deficiencies, Paladini37 makes the following recommen- Pregnancy offers a key opportunity for diet and lifestyle dations: lower transducer emission frequencies, use harmonic and interventions, as women are often motivated to implement compound imaging with speckle reduction filters, consider changes for their well-being as well as the well-being of their approaching fetus through the four major abdominal areas with infant. There is currently limited information available on which to least subcutaneous fat (periumbilical area, suprapubic area and base clinical recommendations about effective dietary and right and left iliac fossae), consider using the transvaginal lifestyle interventions for overweight and obese pregnant women. approach for assessment of the central nervous system in A recent Cochrane review evaluating interventions to prevent fetuses in vertex presentation, wait for the fetus to be in excessive gestational weight gain concluded that there is not optimal position with a posterior spine and become familiar enough evidence to recommend any one particular interven- with the use of color Doppler to check cardiac inflows and tion.48 A meta-analysis by Thangaratinam et al.,49 which included outflows. In addition to these techniques, the provider should take 44 randomized control trials, evaluated diet, exercise or a into account the increased risk of congenital heart disease in combination approach (diet and exercise) among pregnant women who are obese and the frustratingly low visualization rate. women and demonstrated that dietary and lifestyle Providers should strongly consider a formal fetal echocardio- interventions in pregnancy are effective in reducing gestational graphy by a maternal–fetal medicine specialist or a pediatric weight gain without any adverse effect on fetal outcomes. The cardiologist with expertise in fetal echoes. authors noted that the largest reduction in weight gain was Routine counseling should be modified to incorporate a among the diet-only intervention women (3.84 kg, 2.45 to 5.22 kg; discussion of the increased risk of anomalies and the reduced P 0.001), and the diet-only intervention was noted to likelihood of detecting anomalies that may be present.39 The o significantly reduce the risk of pre-eclampsia (RR 0.63, 95% CI decreased ability to obtain an accurate nuchal translucency may 0.42 to 0.96), gestational diabetes (RR 0.39, 95% CI 0.23 to 0.69) limit the sensitivity of first-trimester screening.40 Patients should and gestational hypertension (RR 0.30, 95% CI 0.10 to 0.88) among also be made aware that traditional serum screening for overweight and obese pregnant women. With all interventions chromosomal abnormalities and open neural tube defects may combined, there was no significant difference in low birth weight not yield accurate results in super obese women, and diagnostic or small-for-gestational-age infants.49 Their findings suggested testing such as amniocentesis may be difficult to perform.41,42 that perhaps interventions focused on diet might be most Ultrasound units should be prepared to allot more time for an effective. The focus during pregnancy for overweight and obese obese patient’s scan and be aware that completion of anatomy women should be on avoiding excessive gestational weight gain may require multiple visits. and implementation of dietary and lifestyle changes that can be Given the inaccuracy of fundal height and increased risk of continued past the postpartum period.43,50,51 Interventions should macrosomia3,4 among the super obese, serial ultrasounds for fetal include a balanced diet, physical activity, nutritional counseling growth should be obtained every 3 to 4 weeks beginning at and continued reinforcement by obstetric provider throughout 24 weeks of gestation. In addition, consideration could be given the pregnancy.43,50,51 Further research is needed among to performing antenatal testing in the super obese gravida given overweight and obese pregnant women to identify the optimal the more than twofold risk of stillbirth.33,35,36 intervention to minimize maternal and fetal complications. Please see Table 2 for a prenatal care checklist for super obese Gestational weight management women. The super obese gravida should be counseled on weight management and appropriate weight gain encouraged through- out the pregnancy.43 In 2009, the Institute of Medicine (IOM) INPATIENT MANAGEMENT released updated guidelines on weight gain during pregnancy A multidisciplinary team, including maternal–fetal medicine, based on prepregnancy BMI.44 The IOM guidelines were anesthesia, nursing, pharmacy, nutrition, physical therapy, cardio- developed to minimize negative health consequences for both logy and pulmonology should be established for inpatient mother and fetus of inadequate or excessive weight gain. The management of the super obese gravida. Difficult intravenous

Journal of Perinatology (2014), 495 – 502 & 2014 Nature America, Inc. Super obesity in pregnancy A Martin et al 499 Table 2. Prenatal checklist for super obese women Table 4. Operating room equipment for the super obese Initial prenatal visit Bariatric OR table with extensions for extra width, if needed Routine prenatal labs including first- or second-trimester Patient moving equipment aneuploidy screening, if applicable Extra long safety belt Baseline CBC, chemistry, liver function tests Extra large sequential compression devices Baseline 24 h urine protein Long instruments Early RGS (repeated at 24–28 weeks if normal) Extra lap pads for packing bowel EKG Deep retractors Consider maternal echocardiogram Extra assistants for additional retraction, if needed Counsel on maternal and fetal risks Consider prophylactic anticoagulation Abbreviation: OR, operating room. Begin planning for inpatient hospitalization

Ultrasound hospital beds, primary consideration should be on maximum Counsel on limitations of ultrasound weight accommodation, with bariatric beds ranging from 600- to Early ultrasound for viability and dating and nuchal translucency, if 1000-lb weight capacity.52,53 Many bariatric beds come with applicable pressure redistribution air surfaces that automatically adjust to Refer for serial growth scans starting at 24 weeks patient’s weight, body type and movement to help prevent Consider fetal echocardiogram pressure ulcers. Most standard labor beds accommodate up to Consider antenatal testing starting at 32 weeks 500 lb.53 Special arrangements need to be made if a vaginal delivery is planned for a patient weighing 4500 lb. Ideally, doorways should Multidisciplinary team 52 Referral to cardiology or pulmonology, if suspect underlying be over 3 feet wide. Lifting equipment is essential to avoid staff cardiopulmonary disease and patient injuries. Bariatric lifts can cost anywhere from $2000 to Maternal–fetal medicine $6000.52 Portable or ceiling mounted patient lift systems are Antepartum consult with anesthesiology acceptable.52 The toilet should be placed toward the center of the Nutritionist wall to allow room on each side of the commode for assistants.52 Pharmacy for proper dosing of anticoagulation, antibiotics or Toilets should be anchored to the floor, not the wall. The most other medications common solution on the market today is floor-mounted stainless 52 Abbreviations: CBC, complete blood count; EKG, electrocardiography; RGS, steel toilets with a capacity of 5000 lb. Bathroom walls should rapid glucose screen. have extra strength blocking to support grab bars, as well as sinks that are capable of supporting the extra weight.

Table 3. Hospital equipment for the super obese Mode of delivery Elevator to accommodate bariatric bed with 6000 lb weight limit The cesarean section rate approaches 50% for the morbid and Doorway 43 feet wide super obese.3,4 Failure to progress and failed trial of labor after Bariatric wheelchair cesarean section is more common among these women.54,55 Extra large blood pressure cuff Extra large sequential compression devices Elective primary cesarean sections are also increased. In one study, 33.8% of nulliparous super obese women underwent a scheduled Bariatric hospital and delivery bed 4 Patient lifting system, floor or ceiling mounted acceptable primary cesarean delivery. The indication for these primary Floor anchored toileta cesarean deliveries is not stated, but may be obesity itself. Often in Sink that supports extra weight the super obese gravida, a large pannus and severe lower extremity lymphedema limits range of motion and access to the aShould be in the middle of the wall to allow for assistance on either side. perineum, making safe vaginal delivery essentially impossible. Continuous fetal monitoring and performing a STAT cesarean access is commonly encountered among super obese women and section may be limited or even impossible because of the body placement of peripherally inserted central catheter should be habitus of the super obese gravida. A frank discussion of some of considered. If the patient is not anticoagulated, risks and benefits the clinical limitations should be reviewed with the patient. The of inpatient anticoagulation should be addressed after admission. mode and timing of delivery should be individualized, weighing the risks to the fetus and mother. Transportation and hospital equipment Intraoperative preparation In addition to a medical workup, plans should be made to ensure Preparation for surgery in the extremely obese patient should your facility can accommodate the super obese patient. These include many of the same guidelines as for ideal body weight patients often have limited capability for transportation to and patients. However, additional or special equipment is necessary from the hospital, greatly compromising their need for prompt to facilitate a safe delivery. A standard surgical table accom- arrival in case of emergency. In such cases, hospitalization should modates 350 to 500 lb and therefore a special bariatric surgical be considered. Very often, these patients exceed weight limits for table with a weight capacity of 600 to 1000 lb is necessary.53 standard ambulances and specialized transportation may be Many of the bariatric tables include extensions for greater width if needed. necessary.53 Other intraoperative equipment to have readily Additional things to consider include elevators, wheelchairs, beds, available includes extra large sequential compression devices, doorways, lifting equipment, bathrooms and operating room large safety belts, retractors for subcutaneous fat such as the equipment (Table 3). A 6000- to 6500-lb capacity elevator is needed Alexis O C-section retractor or more traditional retractors deep to provide sufficient space for a 40-inch-wide, 90-inch long bed as retractors (Table 4). many of these patients are transported in their beds.52 Elevators of this size can hold the obese patient, bed, equipment and two staff members.52 Bariatric wheelchairs are sized by weight-limit Anesthesia considerations categories. The largest models can have seat widths of up to 48 The American College of Obstetricians and Gynecologists (ACOG) inches and require a 6-foot or larger turning radius.52 With regard to recommends early referral for anesthesia consultation in the

& 2014 Nature America, Inc. Journal of Perinatology (2014), 495 – 502 Super obesity in pregnancy A Martin et al 500 management of obesity in pregnancy.5 Ideally, a consultation Consideration has been given to increasing the cefazolin dose should be scheduled before the time of delivery to assess if to 3 g for super obese patients. Ho et al.59 calculated serum additional testing is warranted such as pulmonary function tests, cefazolin concentrations at 30, 120 and 360 min after echocardiogram or sleep apnea studies. Because of obscured administration of either 2 or 3 g in morbid (BMI 40 to anatomic landmarks, increased skin to epidural space depth and a 50 kg m À 2) and super obese (BMI 450 kg m À 2) patients. They more narrow epidural space in super obese patients, regional found levels above the minimum inhibitory concentration anesthesia can be very difficult and occasionally unattainable.56 necessary for elective surgical prophylaxis (8 mgmlÀ 1) in both Preoperatively, the anesthesiologist can perform a physical exam patient BMI groups receiving 2 and 3 g doses.59 Although a 3 g and should assess if regional anesthesia is feasible. The dose of cefazolin is safe for patients with a BMI 450 kg m À 2, their anesthesiologist may use ultrasound to help determine the data suggest that a 2 g dose provides sufficient exposure.59 length of epidural or spinal needle required.57 It should also be Although these studies address women with BMI of 450 kg m À 2, noted that one of the reasons for the failure of an epidural there are no studies addressing patients with BMIs approaching catheter to provide adequate block has been the greater risk of 100 kg m À 2. After consultation with our obstetric clinical catheter dislodgement in the obese parturient.56,57 Care should be pharmacist, the decision was made to give 3 g of cefazolin with taken to avoid dislodgement during patient transfer or change of plan for a repeat dose if operating time was 43 h or estimated positions. Secondary to increased risks of general anesthesia, a blood loss was 41500 ml. functioning epidural should ideally be attempted in women during early labor or before scheduled cesarean delivery. The risk Skin incision of failed epidural is increased, with B75% of morbidly obese The ideal surgical skin incision (transverse or vertical) in obese gravidas requiring more than one attempt and 14% requiring over pregnant women is controversial. The advantages to a transverse three attempts for successful epidural placement.56,58 incision include increase wound strength, decreased postopera- If general anesthesia cannot be avoided, the obstetrician and tive pain and improved postoperative respiratory effort,7 however, anesthesiologist should be aware of the increased risk of difficult the concern is for increased infection if placed under a large or failed tracheal intubation in obese pregnant women. Difficult pannus. The advantages to a vertical incision include better intubation rates in obese pregnant women have been reported surgical access and better visualization by the patient for to be as high as 33%,57 and this is likely increased further in postoperative care. However, this incision is more painful, has the super obese. Fat deposition in the neck, back and airway decreased strength with increase likelihood of dehiscence and often precludes optimal positioning of the laryngoscope, herniation and is more likely to require vertical hysterotomy.7,62 and underlying respiratory disorders and weight of the chest There are currently no randomized control trials comparing the wall decreases residual lung volume and functional residual two incision types in morbidly or super obese parturients. When capacity.57,58 Furthermore, excess body weight increases oxygen deciding on an incision type, the surgeon needs to assess the consumption and CO production.56 All of these physiologic 2 anatomy closely, including location of symphysis pubis, iliac wings changes in the obese patients make them more susceptible to and uterine fundus. In our case we opted for a supraumbilical rapid desaturation during intubation.57 In anticipation of a difficult vertical incision as the patient adamantly desired the ability to airway, good preoxygenation should always be performed, and an visualize the incision in order to care for it without assistance at extra pair of skilled hands and emergent airway supplies should home. In addition, given the size of her pannus, we felt that be readily available. To facilitate laryngoscopy, the patient should despite maximum traction we would not be able to adequately be placed in a ‘ramped’ position with blankets under the patient’s retract to safely perform a low transverse incision. thorax and head.56 Perioperative anticoagulation Antibiotic dosing As previously discussed, obesity and cesarean delivery are both Skin cleansing before surgery to reduce bacterial colonization can risk factors for VTE. There is currently no clear evidence regarding be done before surgery, followed by povidine-iodine or chloro- the type of VTE prophylaxis that should be given in obese hexidine preparation covering the entire surgical site in the pregnant women undergoing cesarean delivery. The Royal College operating room. In addition, antibiotic prophylaxis is necessary to of Obstetricians and Gynaecologists (RCOG) in the United reduce risk of postoperative infection. The pharmacokinetics of Kingdom suggests consideration of thromboprophylaxis for 7 antibiotic dosing in patients with super obesity is complicated and days with low-molecular-weight heparin following a normal there are few studies on this topic. Dosing is drug specific because vaginal delivery for those with BMI 440 kg m À 2 and for those of differences in plasma proteins, drug lipophilicity and variations delivered by cesarean with BMI 430 kg m À 2.63 In the United in blood flow to adipose tissue.59 Because of the relative States, the Pregnancy and Thrombosis Working Group did not unpredictability of pharmacokinetics in obese individuals, doses concur with these exact guidelines and instead suggest consi- are best estimated on the basis of specific studies for individual dering thromboprophylaxis for patients who are obese, on bed drugs carried out on this population. The antibiotic of choice for rest or having surgery.64 Morbid and super obesity were not cesarean delivery is cefazolin as it is effective against Gram- specifically addressed. At the very least, early ambulation should positive and -negative bacteria. In a study analyzing serum and be encouraged and mechanical prophylaxis with pneumatic adipose tissue levels of cefazolin given to morbidly obese patients, compression stockings should be used peri- and intra- only when 2 g of cefazolin were administered (versus 1 g) were operatively for all patients. Consideration regarding pharmaco- levels adequate for surgical prophylaxis.60 A more recent study logic thromboprophylaxis should be individualized, and among evaluated serum concentrations of cefazolin in three groups: BMI patients with super obesity who have limited mobility, of 40 to 49, 50 to 59 and 460 kg m À 2. All three groups received thromboprophylaxis should be strongly encouraged. 2 g of cefazolin. In all, 41% of patients with BMI of 40 to 49 kg m À 2 and 18% of those with BMI of 50 to 59 kg m À 2 had serum concentrations that were at the therapeutic threshold 3 h after CONTRACEPTION skin incision, whereas there were no samples from the BMI Contraception should be addressed with every woman of 460 kg m À 2 group at the therapeutic level. Based on these reproductive age, but especially with those who pose significant limited studies, it has been suggested that at least 2 g rather than pregnancy risks such as the morbid and super obese. There are the standard 1 g be used in women with BMI of 435 kg m À 2.61 limited studies including women with BMIs X35 kg m À 2, and no

Journal of Perinatology (2014), 495 – 502 & 2014 Nature America, Inc. Super obesity in pregnancy A Martin et al 501 safety information exists regarding contraception for women 3 Weiss J, Malone F, Emig D, Ball R, Nyberg D, Comstock C et al. Obesity, obstetric specifically with BMIs X50 kg m À 2. Obesity itself is a significant complications and cesarean delivery rate - a population-based screening study. risk factor for VTE, which increases in obese women using Am J Obstet Gynecol 2004; 190(4): 1091–1097. contraceptive methods containing estrogen.65 There have been 4 Marshall N, Guild C, Cheng Y, Caughey A, Halloran D. Maternal superobesity and studies estimating that obese women using oral contraceptives perinatal outcomes. Am J Obstet Gynecol 2012; 206(417): e1–e6. have a 24-fold higher thrombotic risk compared with normal BMI 5 American College of Obstetricians and Gynecologists. ACOG Committee opinion women without use.65 In accordance with Centers for Disease no 549 obesity in pregnancy. Obstet Gynecol 2013; 121(1): 213–217. 6 World Health Organization. Global Database on Body Mass Index 2013. [cited 15 Control and Prevention Medical Eligibility Criteria for Contra- April 2013]. Available from http://apps.who.int/bmi/index.jsp?introPage=intro_3. ceptive Use, all methods of contraception are risk category 1 (no html. restriction for use) except for combined hormonal methods that 7 Gunatilake R, Perlow J. Obesity and pregnancy: clinical managment of the obese are assigned category 2 (advantages of use generally outweigh gravida. Am J Obstet Gynecol 2011; 204(2): 106–119. risks) in healthy obese women with no cardiovascular risk 8 Rosenbaum M, Leibel RL, Hirsch J. Obesity. N Engl J Med 1997; 337(6): factors.66 Category 2 was assigned because of the small 396–407. absolute increased risk of women with BMI X30 kg m À 2 to 9 Bouchard C, Perusse L. Genetics of obesity. Annu Rev Nutr 1993; 13: 337–354. experience VTE while using combined hormonal contraceptives.66 10 Reilly JJ, Armstrong J, Dorosty AR, Emmett PM, Ness A, Rogers I et al. Early life risk Risks to women with BMI of X50 kg m À 2 are not specifically factors for obesity in childhood: cohort study. BMJ 2005; 330(7504): 1357. addressed. 11 Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU et al. Association analyses of 249,796 individuals reveal 18 new loci associated with The American College of Obstetrics and Gynecology (ACOG) body mass index. Nat Genet 2010; 42(11): 937–948. recommends long-acting reversible contraceptive methods, 12 O’Brien TE, Ray JG, Chan WS. Maternal body mass index and the risk of pre- including intrauterine devices (IUDs) and the contraceptive eclampsia: a systematic overview. Epidemiology 2003; 14(3): 368–374. implant, be offered to most women as the first-line contraceptive 13 Brost BC, Goldenberg RL, Mercer BM, Iams JD, Meis PJ, Moawad AH et al. The 67 method. This recommendation includes obese women. Preterm Prediction Study: association of cesarean delivery with increases in Although women 430% above ideal body weight were maternal weight and body mass index. Am J Obstet Gynecol 1997; 177(2): 333–337. excluded from most investigations, a recent study found that 14 Reynolds RM, Osmond C, Phillips DI, Godfrey KM. Maternal BMI, parity, and 3-year failure rates for the implant and IUDs were less than one pregnancy weight gain: influences on offspring adiposity in young adulthood. per 100 women-years.68 Because of the high cesarean section rate J Clin Endocrinol Metabol 2010; 95(12): 5365–5369. among obese patients and potential for difficult office insertion 15 Rooney BL, Mathiason MA, Schauberger CW. Predictors of obesity in childhood, of such devices, strong consideration should be given to adolescence, and adulthood in a birth cohort. Matern Child Health J. 2011; 15(8): 1166–1175. intraoperative placement of IUDs. There have been several 16 Wu Q, Suzuki M. Parental obesity and overweight affect the body-fat accumula- recent studies examining immediate postplacental insertion of tion in the offspring: the possible effect of a high-fat diet through epigenetic IUDs at the time of cesarean section, and the results show a inheritance. Obes Rev 2006; 7(2): 201–208. slightly increased rate of expulsion and lack of visualization of the 17 Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD et al. DNA methy- strings at follow-up, but overall the conclusions are in agreement lation differences after exposure to prenatal famine are common and timing- and that this technique is safe and acceptable.69,70 sex-specific. Hum Mol Genet 2009; 18(21): 4046–4053. 18 Joles JA. 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Journal of Perinatology (2014), 495 – 502 & 2014 Nature America, Inc.