1. Obesity in Pregnancy: Is it a Big Problem? Joseph R. Biggio, M.D.

2. Objectives Become familiar with the physiologic alterations in obese pregnant women Understand the medical and obstetric complications associated with obesity in pregnancy Become familiar with long-term consequences of maternal obesity for the woman and her offspring Discuss risk-reducing strategies for obesity- related complications

3. Obesity Major medical and public health problem Significant morbidity and mortality Health care expenditures: By 2030, 16-18% of all healthcare expenditures related Wang et al, Obesity 2008

4. 2000 Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010 (*BMI 30, or about 30 lbs. overweight for 5’4” person) 2010 1990 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

5. 15%–<20% 20%–<25% 25%–<30% 30%–<35% ≥35% Obesity Among U.S. Adults BRFSS, 2013 CA MT ID NV UT AZ NM WY WA OR CO NE ND SD TX OK KS IA MN AR MO LA MI IN KY IL OH TN MS AL WI PA WV SC VA NC GA FL NY VT ME HI AK NH MA RI CT NJ DE MD DC PR GUAM

7. Obesity in Women NHANES, Health E-Stat, Fryar et al, CDC NCHS, Sept 2014 BMI2001-022011-12 25-29.928.229.7 30-39.933.236.1 >406.58.3

8. Obesity: Race/ethnicity effect NHANES, Health E-Stat, Fryar et al, CDC NCHS, Sept 2014; NCVS, Flegal et al, 2010 2011-12 Non-Hispanic White32.8 Non-Hispanic Black56.6 Asian11.4 Hispanic44.4 75% of AA women BMI >25

9. Economic Costs—Medical Care Increased utilization of resources Prenatal visits Ultrasounds and fetal surveillance Medications dispensed Increased Comorbid conditions Hospitalizations Prolonged hospital stays Maternal and neonatal ICU admissions Adds approximately $5.4-6 billion annually in healthcare cost in UK Chu et al., NEJM, 2008; Heslehurst, Obes Rev 2008; Dennison et al., BJOG. 2009

10. Physiologic Changes: Cardiovascular Blood volume, Cardiac output increase in proportion to fat and tissue mass CO increase 30-35 ml/min per 100 gm fat Diminished progesterone-induced vascular compliance Increase risk for LV hypertrophy Intimal hyperplasia and medial thickening Veille JC et al, AJOG 1994; Perlow J, Obstetric Intensive Care Manual, 2003

11. Physiologic Changes: Pulmonary  PO2, chest wall/lung compliance 50% lower compliance than non-obese Work of breathing 3x higher than normal Risk for sleep apnea Pulmonary hypertension Juvin et al, Anesth Analges, 2003; Perlow J, Obstetric Intensive Care Manual, 2003

12. OSA, Co-morbidities & Outcomes Louis et al, AJOG 2010; 202(3):261

13. Antenatal Complications Infertility Spontaneous Abortion Congenital Malformations Perinatal Mortality

14. Infertility Fecundity reduced Overweight 8% Obese 18% Possible Etiologies HPO axis disruption Increased leptin Insulin resistance with  androgen,  SHBG  fat,  estrone Endometrial abnormalities Gesink et al, Hum Repro, 2007; Pasquali et al, Hum Repro Update, 2003; Haslam, Lancet, 2005

15. Spontaneous Abortion Increased loss rate OR 1.7(1.3 – 2.3) After ovulation induction: OR5.1 (1.8 – 14.8) ? Related to  estrogen and luteal phase defect with  progesterone ? diabetes Metwally et al, Fertil Ster, 2008

16. Congenital Anomaly and Obesity Multiple studies demonstrate increased risk Multiple different types involved Dose-response relationship Undiagnosed diabetes suggested as potential contributor Stothard et al, 2009; Shaw et al, 2008; Biggio et al, 2010

17. Blomberg & Kallen, 2010 Obesity and Anomalies BMI ≥30 NTD2.04 (1.5-2.7) Cardiac1.17 (1.1-2.2) Cleft1.26 (1.1-2.0) Anal atresia1.87 (1.4-2.5) Cystic kidney1.40 (1.0-1.9) Omphalocele2.03 (1.4-2.9)

18. BMI 30-34.935-39.9≥40 NTD1.8 (1.3-2.5)2.1 (1.1-3.5)4.1 (1.9-7.8) Cardiac1.1 (1.0-1.2)1.3 (1.1-1.4)1.5(1.2-1.8) Cleft1.1 (0.9-1.3)1.6 (1.3-2.1)1.9 (1.3-2.9) Anal atresia1.8 (1.3-2.4)1.5 (0.7-2.6)3.7 (1.7-7.1) Dose-Dependent Blomberg & Kallen, 2010

19. Perinatal Mortality Adjusted OR* Cedergren – Obstet Gynecol 2004 19.8 – 26.0 29.1 – 35.0 35.1 – 40.0 BMI (kg/m 2 ) > 40.0 Stillbirth after 28 weeks Early Neonatal Death

20. Perinatal Complications Preeclampsia Preterm birth Gestational diabetes Fetal macrosomia Fetal Demise

21. Pre-eclampsia Adjusted OR* Cedergren – Obstet Gynecol 2004 19.8 – 26.0 29.1 – 35.0 35.1 – 40.0 BMI (kg/m 2 ) > 40.0

22. Pre-eclampsia Each BMI unit increases risk 0.5% Normal weight 2-4% BMI ≥ 308-12% Similar magnitude regardless of race Bodnar et al, Epidemiology, 2007 O’Brien et al, Epidemiology, 2003

23. Preterm Birth Conflicting literature Multiple studies suggest protective against SPTB Obesity characterized by inflammation Large meta-analysis of overweight and obese women PTB <37 wkRR 1.06 (0.87 – 1.3) SPTBRR 0.93 (0.85 – 1.01) Indicated PTBRR 1.30 (1.23 – 1.37) McDonald et al, 2010

24. Preterm Birth Swedish Birth Registry SPTB Extremely PTB (22-27 wk) increases with BMI No increase in 28-31 or 32-36 wk Indicated PTB Increased for all GA and all BMI >25 Highest risk BMI ≥40 BMI 25-<3030-<3535-<40≥40 1.12 (1.0-1.2)1.22 (1.04-1.44)1.73 (1.35-2.21)2.71 (1.95-3.78) Cnattingius et al, 2013

25. Gestational Diabetes Odds Ratio Sebire 2001 20 - 24.9 25 – 29.9 BMI (kg/m 2 ) >30

26. LGA/Macrosomia Odds Ratio Cedergren, Obstet Gynecol, 2004 29.1 – 35 35.1 – 40 BMI (kg/m 2 ) >40

27. Mechanism unclear Meta-analysis Overweight1.5 (1.1 – 1.9) Obese2.1 (1.6 – 2.7) Translate to 1.4% SB rate Ethnic disparity in risk Caucasian1.4 (1.3 – 1.5) AA1.9 (1.7 – 2.1) Chu et al, 2007 Salihu et al, 2007 Fetal Demise

28. Stillbirth Collaborative Network Obesity/overweight independently associated aOR 1.72 (1.22 – 2.43) Danish Birth Cohort 28-36 wkHR 2.1 (1.0 – 4.4) 37-39 wkHR 3.5 (1.9 – 6.4) ≥40 wkHR4.6 (1.6 – 1.3) Stillbirth Network, 2011; Nohr et al, 2005

29. Peripartum Complications Labor induction Cesarean delivery Labor dysfunction Postpartum hemorrhage Shoulder dystocia Wound complications Neonatal complications

30. Induction of Labor Cedergren, Obstet Gyncecol, 2004 Odds ratio

31. Cesarean Delivery Cedergren, Obstet Gyncecol, 2004 Odds ratio

32. Cesarean: Wound Infections 100 – 199 lb 200 – 299 lb ≥ 300 lb < 100 lb % Women with Wound Infections NICHD MFMU C/S Registry 2002 p < 0.0001

33. C/S Contributors Inductions Co-morbidities Presumed macrosomia Fetal decompensation intrapartum Dysfunctional labor 3.5X rate of CS in first stage of labor Increased need for augmentation and higher doses of oxytocin In vitro—poor myometrial contractility Zhang et al, BJOG, 2007

34. Postpartum Hemorrhage Cedergren, Obstet Gyncecol, 2004 Odds ratio

35. Anesthesia risks Failed intubation 4-6x Soft tissue mass Ventilation difficulties Breast mass Decreased lung volumes Failed /difficult regional Juvin et al, Anesth Analges, 2003; Jordan et al, AJOG, 2004

36. Long-term Risks Increasing maternal obesity Co-morbidities Developmental origins of obesity Childhood obesity Metabolic syndrome

37. Post-Partum Weight Retention Gestational weight gain retention Mean 11.8 lb at 6 months GWG > IOM 15 – 20 lb retention >40% of women with >20 lb retention >50% overweight women are obese by 1 yr postpartum IOM, 2009; Gould Rothberg, AJOG, 2011

38. Breastfeeding Obese women less likely to breastfeed BMI 25-300.86 (0.84 – 0.88) BMI >300.58 (0.56 – 0.60) Missed potential benefits Maternal Infant Sebire et al, Intl J Obesity, 2001; Li et al, Am J Pub Health, 2002

39. Childhood Obesity Maternal obesity correlates with neonatal fat mass Obesity in offspring of obese mothers BMI >95 th percentile at ages 2-4 OR 2.4 – 2.7 ↑ Central obesity, lipid abnormalities, hypertension–age 7 Whitaker RC, Pediatrics, 2004; Oken et al, AJOG, 2007; Catalano et al, AJOG 2003, 2004

40. Summary of Problem Scope of the problem is far-reaching Pregnancy Life-long Next generation

41. Optimizing Perinatal Outcomes

42. Initial Antepartum Evaluation Assessment for co-morbidities Metabolic syndrome: Hypertension Glucose intolerance/Diabetes Hyperlipidemia Sleep apnea Early dating US Oligo-ovulation LMP unreliable

43. Optimizing Outcomes: Gestational Weight Gain Education Dietary Intake Exercise Set goals and plot weight gain Only ~250 kcal/d increase needed for normal weight

44. Optimizing Outcomes: Gestational Weight Gain Total Weight Gain 11-20 lb 0.5 lb/wk in 2 nd & 3 rd trimesters Nearly 2/3 of obese women exceed recommended GWG

45. Gestational Weight Gain Excess weight gain associated with Macrosomia Operative delivery NICU Weight gain <15 lb associated with lower rates of: Pre-eclampsia Cesarean LGA/SGA Kiel et al, 2007

46. Pre-E: Effect of Weight Gain Overweight and Obese women Weight gain <15 lbOR 0.5 – 1 > 25 lbOR 1.2 – 1.7 Kiel et al, 2007

47. Optimizing Outcomes: Early GDM Screening Lack of evidence of cost-effectiveness Target population Previous history GDM Family history of DM Prior macrosomic infant Treatment may lower risks HgbA1C and risk assessment for other complications Catalano, 2007

48. Optimizing Outcomes: Reducing pre-eclampsia Patients with GDM—Improved glycemic control, lower risk pre-e ACHOIS—18% vs 12% MFMU—13.6 % vs 8.6% Landon et al, 2009; Crowther et al, 2005

49. Optimizing Outcomes: OSA CPAP Improves symptoms, mood BP, pre-eclampsia Birthweight Minimize use of narcotic pain relief Anesthesia consultation If not confirmed, monitor O2 sats Sleep Medicine referral Franklin et al, 2000; Poyares et al, 2007; Guilleminault et al, 2007

51. Anatomic Assessment U/S Visualization Completion of anatomic assessment declines with increasing BMI 10% decrement per obesity class Dashe et al, 2009; Thornburg et al, 2009; Weichert and Hartge, 2010; Hendler et al, 2004; Becker and Wegner, 2006 <2525-29.930-34.935-39.9≥40 Basic72%68%57%41%30% Targeted97%91%75%88%75%

52. Dashe et al, 2009; Aagaard et al, 2010 Detection rate decreases with increasing BMI Residual anomaly risk increases with BMI FASTER Trial Detection aOR 0.70 (0.6-0.9)

53. Optimizing Outcomes: Anatomic Assessment 11-14 week scan Lack of evidence in obese women Combined TA and TV approach 82% complete anatomy 3.7% anomaly detection 84.2% heart defect detection Ebrashy et al, 2010; Becker and Wegner, 2006

54. Optimizing Outcomes: Prenatal Diagnosis NIPT Fetal fraction lower Adipose cell death Inflammation Redraw rates Diagnostic Procedures BMI ≥40 2-fold increase loss after amnio Ashoor et al, 2013; Haghiac et al, 2012; Harper et al, 2012

55. Fetal Fraction in Relation to BMI Ashoor et al, 2013

56. Optimizing Outcomes: Growth Surveillance Macrosomia 2-fold increase IUGR Mainly in women with hypertension or pre-eclampsia Fundal height Limited accuracy Biometry q4-6 weeks Ehrenberg et al, 2004; Neilson, 2000; Morse et al, 2009; ACOG CO #549, 2013

57. Optimizing Outcomes: Antenatal Testing Placental histology Placental dysfunctionOR 5.2 Vigilance for hypertension, diabetes Antenatal surveillance Even in absence of other indications Catalano, 2007; Nohr et al, 2005

59. Optimizing Outcomes: Mode of Delivery Labor dysfunction Increased oxytocin dose 5.0 units vs 2.6 units Longer labor duration 8.5 vs 6.5 hours Impaired myometrial contractility Leptin inhibitory effect Not oxytocin receptor mediated Pevzner et al, 2009; Quenby wt al, 2011; Zhang et al, 2007, 2011; Moynihan et al, 2006; Grotegut et al, 2013

60. Vaginal vs Cesarean Swedish birth registry Neonatal outcomes by mode of delivery 2-4 fold increase for BMI ≥40 : Birth injury RDS Sepsis Hypoglycemia Similar risk vaginal vs. elective cesarean Blomberg, 2013

61. Optimizing Outcomes: Mode of Delivery Lack of evidence Factors to consider Increased need for cesarean Ability to monitor fetal status Time from skin to delivery increased Gunatilake and Perlow, 2011

62. VBAC Success MFMU Cesarean Registry >14,000 VBAC attempts Hibbard et al, 2006 18.5-24.925.0-29.930-39.9≥40p Failed TOL15.222.329.939.3<0.001 LOS ≥4d9.413.018.930.3<0.001 Endometritis1.62.63.04.6<0.001 Rupture/ dehiscence 0.91.51.42.10.03

63. Reduces risk of puerperal fever Endomyometritis Wound infection Weight-based dosing modification Cefazolin ≤80 kg1 gm 81-160 kg2 gm ≥160 kg3 gm Perioperative Antibiotics JCAHO, SCIP recommendations; Smaill et al, 2010;

64. Cefazolin in obese 29 scheduled C/S; 2 gm cefazolin Adipose concentration inversely related to BMI BMI ≥3020% less than MIC for GNR BMI ≥40up to 44% less than MIC Pevzner et al, 2011

66. Optimizing Outcomes: Intraoperative management Incision type Fascial Closure Subcutaneous closure Appropriate Equipment Bed Instruments Transfer apparatus

67. Incision Type and Placement Pfannenstiel –Less adipose depth –Access to LUS –More stable closure –Moist, anaerobic, microbe-rich –Cava compression –Respiratory impairment intraop Vertical Avoid under pannus More room Cut through thicker part of panniculus Placement difficult Increased likelihood of vertical hysterotomy Pulmonary issues post Less stable closure Wall et al,2003; Alanis et al, 2010; Bell et al, 2011

68. 194 women BMI >50 30% wound complication Vertical incisionOR 2.2 (1.2 – 4.3) 239 women BMI > 35 12% wound complication Vertical incisionOR 12.4 (3.9 – 39.3) Pfannenstiel vs Vertical Alanis et al, AJOG, 2010; Wall et al, Obstet Gynecol, 2003

69. Optimizing Outcomes: Subcutaneous Space Management Meta-analysis Depth >2 cm Wound disruptionRR 0.66 (0.48-0.91) Reduction in wound seroma RR 0.42 No added benefit to drain Chelmow et al, 2004; Magann et al, 2002; Ramsey et al, 2005

70. Optimizing Outcomes: Intrapartum management Minimize induction of labor, as possible Anticipate longer length of labor and need for higher doses of oxytocin Early epidural placement for analgesia Decision on best mode of delivery Fetal monitoring capability Prior C/S EFW

71. Optimizing Outcomes: Intrapartum management Prophylactic cesarean considered for macrsomia Prepare for pp hemorrhage regardless of mode of delivery Choose surgical approach and instruments to facilitate exposure and technique ACOG Practice Bulletin 22, 2000

72. Optimizing Outcomes: Thromboprophylaxis Obesity major risk factor OR 4.4 (3.4 – 5.7) for VTE No RCT with benefit of UFH vs LMWH vs pneumatic compression device At least one form recommended High risk patients--heparin plus pneumatic Vascular disease, thrombophilia, severe pre-e Early ambulation James et al, 2006; Bates et al, 2008; Tooher et al, 2010

74. Obesity is associated with an increased risk of a number of maternal obstetric and medical complications Good evidence is available to minimize the risk of many complications associated with obesity Although data are lacking on how to prevent a number of these complications, careful preparation and anticipation may minimize the risks and improve outcomes in the current and future pregnancies Summary