November 09, 2013 Create your Plate Method (5) 5. Add an 8 oz. glass of non-fat or low-fat milk. • If you don't drink milk, you can add milk, you can add another small serving of carb such as a 6 oz. container of light yogurt or a small roll. Website American Diabetes Association. Create your Plate Method (6) 6. Add a piece of fruit or a 1/2 cup fruit salad and you have your meal planned. • • Examples are fresh Examples are fresh, frozen, or canned in juice or frozen in light syrup or fresh fruit. Website American Diabetes Association. Lunch and Dinner MyPlate for Gestational Diabetes. Sweet Success. California Diabetes and Pregnancy Program. January 17, 2013. 13
November 09, 2013 Meal Measure Shopdiabetes.org Breakfast • Insulin resistance is usually greater in the morning. • Breakfast carbohydrate load may need to be restricted to 15-30 grams. • Fruit juices, fruits, milk, ready-to-eat or instant cereals, bagels, and croissants are usually excluded. • Individual tolerance determined by self blood glucose monitoring. Website American Diabetes Association. MyPlate for Gestational Diabetes. Sweet Success. California Diabetes and Pregnancy Program. January 17, 2013. 14
November 09, 2013 Fruit: Carbs A B C 1 Cup Carbs (g) 1 Cup Carbs (g) 1 Cup Carbs (g) Strawberries 11.1 Peaches 16.2 Pear 25.5 Watermelon 11.5 Apple 17.3 Kiwi 26.0 Avocado 12.5 Grapefruit 18.6 Grapes 27.9 Mango 28.1 Cantaloupe 13.1 Plum 18.8 Papaya 13.7 Blueberries 21.0 Banana 34.3 Blackberries 13.8 Oranges 21.2 Raisins 114.8 Raspberries 14.7 Honeydew 15.5 Fatsecret.com/calories-nutrition MyPlate for Gestational Diabetes. Sweet Success. California Diabetes and Pregnancy Program. January 17, 2013. Sample Daytime Snacks • ½ toasted English muffin with 1 Tbsp natural style peanut butter • 1 quesadilla (1 small tortilla and 1 ounce cheese) • 1 cup melon with ¼ cup cottage cheese • 1 small apple (cut into slices) with 1 Tbsp natural-style peanut butter • 2 Tbsp sunflower seeds and 2 Tbsp raisins • ½ turkey or ham sandwich • 6 saltine crackers with 1 ounce tuna Website American Diabetes Association. 15
November 09, 2013 Sample Bedtime Snacks • 2/3 cup rice with 1 ounce meat, chicken or fish • 1 small tortilla with 1 ounce meat and ½ cup beans • 1 ham or turkey sandwich • 1 cup sugar-free yogurt and ½ peanut butter sandwich • 1 cup milk and ½ toasted English Muffin with melted cheese and sliced tomatoes • 1 cup milk with a mini sandwich (1 ounce dinner roll and 1 ounce sandwich meat or cheese) Website American Diabetes Association. Individualize the Plan! • Patient-centered care is defined as an approach to ‘providing care that is respectful of and responsive to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions’ • In order to maximize our efforts � Address cultural issues � Address personal health beliefs Committee on Quality of Health Care in America: Institute of Medicine, 2001. Inzucchi SE et al. Diabetologia (2012) 55:1577–1596. Tortilla: Size 6-inch 8-inch 10-inch 12-inch Calories 94 144 218 356 Fat (g) Fat (g) 2 32 2.32 3.56 3 56 5.42 5 42 9 9 Carbs (g) 15.4 23.6 35.94 59 Protein (g) 2.49 3.81 5.8 9 Fatsecret.com/calories-nutrition 16
November 09, 2013 Tortilla: Type White Whole 6-inch Corn flour wheat Calories 58 94 71 Fat (g) Fat (g) 1 1 2.32 2 32 0 35 0.35 Carbs (g) 12 15.4 15.07 Protein (g) 1 2.49 2.59 Fatsecret.com/calories-nutrition Rice: Type 1 cup White Brown Sticky cooked Calories 242 215 169 Fat (g) Fat (g) 0 35 0.35 1 74 1.74 0 33 0.33 Carbs (g) 53.4 44.4 36.7 Protein (g) 4.4 5.0 3.5 Fatsecret.com/calories-nutrition Lifestyle Intervention Regular Nutrition + Therapy Exercise • The cornerstone of management for T2DM • At least 150 minutes/week of moderate-intensity aerobic physical activity Inzucchi SE et al. Diabetologia (2012) 55:1577–1596. 17
November 09, 2013 Exercise in Pregnancy • ACOG recommends that pregnant women engage in 30 minutes or more of moderate exercise on most, if not all, days of the week – Both aerobic and strength conditioning exercises are encouraged in g g g pregnant women without complications – Sedentary women, start with 15 minutes of continuous exercise 3 times per week, gradually increasing to 30 minutes per day (for a total of 150 minutes per week) ACOG Committee Opinion, Number 267, January 2002 (Reaffirmed in 2009). Exercise in Pregnancy • Exercise should include a 5-10 minute warm-up and a cool-down period • Moderate intensity – Talk test – One can talk, but not sing, during the activity ACOG Committee Opinion, Number 267, January 2002 (Reaffirmed in 2009). ACOG FAQ0119 Pregnancy. Center for Disease Control and Prevention. Measuring Physical Activity Intensity. December 1, 2011. Exercise • Avoid high impact or excessively jarring exercises and contact sports • Minimize the risk of loss of balance/falling and abdominal • Minimize the risk of loss of balance/falling and abdominal trauma • Heavy weightlifting, or similar activities that require straining, are to be discouraged. ACOG Committee Opinion, Number 267, January 2002 (Reaffirmed in 2009). The American College of Sports Medicine. Current Comment: Exercise in Pregnancy. 18
November 09, 2013 Exercise • Walking • Treadmill walking • Low impact aerobics • Step aerobics (until uterus blocks vision of step) • Water aerobics • • Swimming Swimming • Stepping Machine (including elliptical) • Bicycling (only in early pregnancy) • Stationary bicycling • Dancing • Yoga • Light weight training • General gardening ACOG Committee Opinion, Number 267, January 2002 (Reaffirmed in 2009). CDAPP Sweet Success Guidelines for Care. Chapter 6. Exercise. 2012. Lifestyle Intervention Overview • Eat 3 meals and 3 snacks, 2-3 hours apart • Bedtime snack so that no more than 10 hours pass b f before breakfast b kf t • Plenty of fluids (caffeine-free, sugar-free). • Walk 10-15 minutes after each meal MyPlate for Gestational Diabetes. Sweet Success. California Diabetes and Pregnancy Program. January 17, 2013. Clinical Recommendations: Diabetic Diet 1) Know your patient’s obstacles in adhering to a diabetic diet • Addressing cultural issues and personal health beliefs will help to maximize your efforts 2) Use MyPlate when discussing/reviewing the diabetic diet 3) Exercise is an important adjunct in diabetes management 19
November 09, 2013 Screening and Diagnosis of Gestational Diabetes Adi Abramovici, M.D. Assistant Professor, Division of Maternal ‐ Fetal Medicine 20
November 09, 2013 Gestational Diabetes Screening and Diagnosis: The Whom, When and How Adi Abramovici, M.D. Division of Maternal Fetal Medicine University of Texas Health Science Center at Houston Disclosure Statement I do not have relevant financial relationships with commercial interests related to the content of this presentation. Objectives • Discuss how to screen and diagnose Gestational Diabetes Mellitus (GDM) • Recognize common challenges when screening/diagnosing GDM 21
November 09, 2013 Why Screen? • Prevalence 6 ‐ 7% in the United States � 240,000 of 4 Million annual births • Lifetime risk of Type 2 DM: 50% • Increased Risk: � Preeclampsia � Fetal macrosomia � Neonatal hypoglycemia Am J Obstet Gynecol 192:1768–1776, 2005 Diabetes Care 31(S1) 2008 Gabbe, Obstetrics: Normal and Problem Pregnancies 2002 Who Is At Risk? • Family Hx • Obesity • Age >25 years • Previous delivery >9 pounds Previous delivery >9 pounds • Hx Impaired glucose tolerance • Hispanic/African American 4 th International Workshop Conference on Gestational Diabetes Mellitus. 1997 Marion DW. Screening and Diagnosis of gestational diabetes mellitus. UpToDate Website . Who Is At Risk? • Unexplained perinatal loss/malformed infant • Maternal birth weight >9 pounds • Glycosuria at the first prenatal visit • Polycystic ovary syndrome Polycystic ovary syndrome • Current use of glucocorticoids • Essential hypertension • Metabolic syndrome 22
November 09, 2013 Whom Should Be Screened? • In the United States, universal screening appears to be the most practical approach • Up to 20 percent of women diagnosed with GDM have no risk factors • ACOG recommends Universal Screening Practice bulletin no.137: Gestational diabetes mellitus. When to Screen? • ACOG recommends: � High Risk: First Prenatal Visit � Universal screening 24 ‐ 28 weeks Practice bulletin no.137: Gestational diabetes mellitus. Early Screening? • Prior GDM • Known impaired glucose tolerance • Obesity BMI >30 Practice bulletin no.137: Gestational diabetes mellitus. 23
November 09, 2013 How to Screen? • There is no worldwide standard for screening and diagnosis of diabetes during pregnancy. • In the United States, the most common approach is: 2 ‐ step approach Practice bulletin no.137: Gestational diabetes mellitus. 2 ‐ Step Approach • Step 1: � Give 50 gram oral glucose load � Glucose: � Glucose: ≥ 130 mg/dL (per Carpenter/Coustan) ≥ 135 mg/dL or ≥ 140 mg/dL (per ACOG) • Step 2: � Administration of a full glucose tolerance test Which Cutoff is Best? Threshold Sensitivity Specificity 130 88 ‐ 99% 66 ‐ 77% 135 80 ‐ 90% 67 ‐ 80% 140 70 ‐ 88% 69 ‐ 89% Donovan L. Screening tests for gestational diabetes: A systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013. 24
November 09, 2013 100 gram 3–hour GTT • Recommended by ACOG/2013 NIH Consensus Conference • 2 Elevated values = positive test • Carpenter/Coustan vs. National Diabetes Data Group thresholds • Consider eliminating if 1 ‐ Hour >190 ‐ 200ng/dL 2 diagnostic criteria for 3 ‐ hour GTT Carpenter/Coustan NDDG Fasting 95 105 One hour 180 190 T Two hours h 155 155 165 165 Three hours 140 145 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diab Care 2000; 23(suppl 1):S4. 1 ‐ Step Approach • 75 gram two ‐ hour oral GTT • Administered at 24 to 28 weeks of gestation • Omits the screening 50 gram glucose • Not Endorsed by ACOG 25
November 09, 2013 75 ‐ gram GTT • HAPO Study • Adverse outcomes � Macrosomia � Macrosomia � Cesarean delivery � Neonatal hypoglycemia � Preeclampsia HAPO Study Cooperative Research Group, Metzger BE. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008. The 2013 NIH Consensus Conference recommended against adoption of the one step approach and criteria because it would increase the prevalence of GDM, leading to increase the prevalence of G M, leading to more frequent prenatal visits, more fetal and maternal surveillance, and more interventions, including induction of labor, without clear demonstration of improvements in the most clinically important health and patient ‐ centered outcomes. Challenging Scenarios • Early screening? 2 ‐ Step vs. Fasting vs. HgA1C • Early abnormal 1 ‐ hour, normal 3 ‐ hour? • Counseling regarding diet/fasting prior to screening? • Special considerations � Bariatric patients � Inability to tolerate glucose 26
November 09, 2013 SUMMARY AND RECOMMENDATIONS • Universal screening • Screening 24 ‐ 28 weeks using a 2 ‐ step approach • Cutoffs: � 1 Hour: 135 mg/dL � 3 Hour: 95/180/155/140 mg/dL • High Risk Women: � Screen 1 st Visit � If negative: Repeat 24 ‐ 28 weeks Questions? 27
November 09, 2013 Glycemic Control During Pregnancy: What Are Our Targets? Clara Ward, M.D. Assistant Professor, Division of Maternal ‐ Fetal Medicine 28
November 09, 2013 Glycemic Control During Pregnancy: What are our targets? Clara Ward, MD Assistant Professor Division of Maternal Fetal Medicine Department of Obstetrics, Gynecology, and Reproductive Sciences Objectives • How do we assess glycemic control at presentation? • How do we assess glycemic control throughout gestation? throughout gestation? • Why does it matter? • What should our targets be? Objectives • HbA1c • Glycemic Targets – Background – What numbers – Definitions – When to check – Targets – Which values matter – Significance – What is good control – Caveats – Special circumstances 29
November 09, 2013 Hemoglobin A1c • Represents mean glucose concentration over prior 8 ‐ 12 weeks • Weighted average • More emphasis on last 30 days • More emphasis on last 30 days • Marker of disease control • HbA1c of 8% � mean serum glucose 180 • Each 1% � 30 mg/dL ADAG Study 2008. Diabetes Care; 31:1 ‐ 6 Hemoglobin A1c • Normal: ≤ 5.6% • Pre ‐ diabetes: 5.7 ‐ 6.4% • Overt diabetes: ≥ 6.5% • Goal non ‐ pregnant: <7.0% • Diabetes Complications and Control Trial (DCCT) • United Kingdom Prospective Diabetes Study (UKPDS) • Goal pregnant/pre ‐ conceptional: <6.0% Hemoglobin A1c Mosca 2006. Clinical Chem 52(6): 1138 ‐ 1143 30
November 09, 2013 Hemoglobin A1c • Correlated with adverse pregnancy outcomes • Spontaneous abortion • Congenital anomalies • Intrauterine fetal demise • Preterm labor • Macrosomia • Shoulder dystocia • Preeclampsia • Maternal complications of diabetes Hemoglobin A1c . Ylinen et al. 1984. BMJ 289: 345 ‐ 6. Lapolla et al, 2010. Acta Diabetol 47:187 ‐ 9.2 Hemoglobin A1c Jensen et al 2009. Diabetes Care 32:1046–8. Lapolla 2010. Acta Diabetol 47:187 ‐ 92. 31
November 09, 2013 Periconceptional Glycemic Control • Fasting <120 • Preprandial <140 • Preprandial <140 • Postprandial <140 • HbA1c <6% Langer and Conway, 2000. JMFM 9: 35 ‐ 41. Hemoglobin A1c: Caveats • Unreliable in pregnancy • Changes in RBC physiology • Does not reflect short term variations • Decreased in pregnancy • False sense of glycemic control g y • Decreased clearance in pregnancy • Unable to accurately assess effect of therapy • Questionable correlation with actual glucose values • Varying laboratory ranges of normal ADIPS 2005. NICE 2008. Murphy 2008. BMJ;337:a1680 Hemoglobin A1c • Risk of perinatal complications decreases with decrease in HbA1c on a population level • However, HbA1c cannot be used to assess risk of adverse perinatal outcomes in individual of adverse perinatal outcomes in individual pregnancy • Correlates with other manifestations of poor control Nielsen, et al 2006. Diabetes Care 29:2612–2616. Evers, et al 2002. Diabetologia 45:1484–1489. 32
November 09, 2013 Hemoglobin A1c Who and when should we test? • GDM • Low yield/not recommended • Occult Type 2 DM • Early identification of glucose intolerance l id ifi i f l i l • Pre ‐ gestational • PNC intake • Repeat measurement • Noncompliant Hemoglobin A1c • Greatest benefit is periconceptional • Assess risk of congenital malformations • Shape approach to counseling • Assess need for admission during organogenesis • Assess need for admission during organogenesis • Preconception care and pregnancy planning reduces morbidity • Define pre ‐ gestational insulin resistance, associated risks, and impact on future health Glucose Monitoring • All pre ‐ gestational and gestational diabetics during pregnancy • Minimum 4 times daily • Fasting F ti • 1 or 2 hours after meal • Logs with DIETARY INFORMATION 33
November 09, 2013 Glucose Monitoring Hawkins et al, 2009. Obstet Gynecol, 113 (6): 1307 ‐ 12 Glucose Monitoring Glucose Monitoring 34
November 09, 2013 Glucose Monitoring • Differential measurement? – Sivan et al. 2001. AJOG 185: 604 ‐ 7. • Postprandial peak at 90 minutes after all meals – Ben ‐ Haroush et al 2004 AJOG 191: 576e81 – Ben ‐ Haroush et al. 2004. AJOG 191: 576e81 • No difference in neonatal or maternal outcomes – Weisz et al. 2005. J Perinatology 25: 241 ‐ 244. Glycemic Targets • Fasting • Goal: ≤ 95 • Preprandial • Goal: <100 G l 100 • Postprandial • Goal: <140 (1 hour) vs. <120 (2 hours) Metzger 2007. Diabetes Care, 30:Supp2. Glycemic Targets • Karlsson and Kjellmer 1972. AJOG 112: 213 ‐ 20. • T1DM • Mean BG <100, 100 ‐ 150, >150 • 3.8%, 16%, and 24% risk of perinatal loss, respectively 3.8%, 16%, and 24% risk of perinatal loss, respectively • Pettitt et al 1980. Diabetes Care 3: 458 ‐ 464. • GDM and T2DM (Pima) • Direct relationship between OGTT and perinatal mortality 35
November 09, 2013 Glycemic Targets • GDM have more perinatal loss than non ‐ GDM • O’Sullivan et al 1973. AJOG 1: 901 ‐ 4 • Perinatal loss most prevalent in those patients with LGA • Pettitt et al 1980. Diabetes Care 3: 458 ‐ 464 • Postprandial BG <140 decreases risk by 75% • Beischer et al 1996. Aust NZ J Obstet Gynecol 36: 239 ‐ 47. • Mean BG <115 reduces risk of perinatal mortality • Langer and Conway 2000. JMFM 9: 35 ‐ 41. Glycemic Targets Langer and Conway 2000. JMFM 9: 35 ‐ 41 Glycemic Targets Langer and Conway 2000. JMFM 9: 35 ‐ 41 36
November 09, 2013 Glucose Monitoring: Which targets are most important? • Gestational vs. Pre ‐ gestational • Fasting vs. Postprandial • Initiation vs. Term Initiation vs. Term BOTTOM LINE: They are all important! Glucose Monitoring: Surveillance • Abnormal GTT (or PNC intake for pregestational) • 1 week of dietary logs and SMBG • Nutritional counseling/diabetic education • Initial assessment of control • If >50% of values above target range • If >50% of values above target range • Reassess in 1 week • Possibility of nutritional modifications • If mild elevations ~15 mg/dL above target • Encourage ambulation after meals/before SMBG • Intensive surveillance • Noncompliant, late to/lapse of care • Self ‐ titration Assessing Control • Weekly review of logs/medication changes • Phone • Fax • Email • Noncompliance • Weekly appointments • Admission • Rewards • Decrease frequency of fingersticks after 35 weeks 37
November 09, 2013 Assessing “Good” Control • Goal is <50% of blood glucose measurements above the target range • Are you eating in the middle of the night? • When did you really check your sugar/take your • When did you really check your sugar/take your insulin? • Can you walk for 15 minutes after meals? • So you had tortillas, cake, ice cream, soda, and gummi worms at your kid’s party? Assessing “Good” Control • “My what good control you have” • Calorie and carbohydrate restriction • Failure to snack • Failure to fake better • Failure to fake better • All glucose values end in 5 or 0 Glucose Monitoring: Special Circumstances • GDMA1 • Reduced frequency if excellent control >35 weeks • Pregestational Diabetes • Preprandial monitoring di l i i • Nocturnal Hypoglycemia • 2 AM check • Alternative Schedules 38
November 09, 2013 Is tighter control better? • Strict 60 ‐ 90 mg/dL vs. Moderate 80 ‐ 116 mg/dL • Risks • Hypoglycemia (<60 mg/dL) • Transient exacerbation of retinopathy • Caveats • What kind of diabetic • Rebound hyperglycemia • Low morale • No significant clinical benefit Middleton 2012, Cochrane Review Are we on target? Langer and Conway 2000. JMFM 9: 35 ‐ 41 Patient Materials • http://www.lillydiabetes.com/Pages/downloa dable ‐ materials.aspx • Meal planning and carbohydrate guide • Log books • Log books • Diabetes spinner: carbohydrate estimation • http://www.diabetescare.net/handouts.asp • UCSF ‐‐ comprehensive 39
November 09, 2013 40
November 09, 2013 Recommendations: HbA1c • Goal HbA1c <6% prior to conception • Pregestational DM: Check HbA1c at PNC intake • Early positive GTT: Check HbA1c at diagnosis l i i G h k b di i • Gestational DM: Don’t check HbA1c • Serial/Routine measurement of HbA1c not recommended Recommendations: Monitoring • Logs: glucose and diet • Fingerstick glucose at every PNC visit • SMBG 4 times daily • Fasting: goal <95 • Postprandial: goal <120 (2 hours) or <140 (1 hour) • Pregestational DM • 2AM or preprandial checks as needed Recommendations: Surveillance • Abnormal GTT (or PNC intake for pregestational) • 1 week of dietary logs and SMBG • Nutritional counseling/diabetic education • Initial assessment of control in 1 week • If >50% of values above target range • Possibility of nutritional modifications • If mild elevations ~15 mg/dL above target • Encourage ambulation after meals/before SMBG • Consider admission if <10 weeks • Intensive surveillance • Noncompliant, late to/lapse of care 41
November 09, 2013 Recommendations: Surveillance • Glycemic control is a continuum • Partnership • Care of the pregnancy complicated by di b diabetes begins preconceptionally b i i ll 42
November 09, 2013 When and What Medications to Use for DM in Pregnancy: Insulin, Glyburide, Metformin, etc. Sean Blackwell, M.D. Chair, Department of Obstetrics, Gynecology and Reproductive Sciences 43
November 09, 2013 What are medication options for the Diabetic Gravida ? Sean C. Blackwell, M.D. Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences Director, Larry C. Gilstrap M.D. Center for Perinatal and Women’s Health Research Assistant Dean for Healthcare Quality in Perinatal Medicine and Women's Health University of Texas Medical School at Houston (UTHealth) Medical School Sean.Blackwell@uth.tmc.edu Objectives • To discuss insulin type and dosing options for women with Type 1 and Type 2 DM. • To evaluate criteria, risks, and challenges for l i i i k d h ll f use of oral hypoglycemic medications for women with T2 and GDM during pregnancy. Case • Ms. Jones is G 4 P 3 here for 1 st prenatal care visit ‐ referred from family practice physician who confirmed pregnancy She has confirmed pregnancy. She has history of T2 diabetes but not on treatment. She is 12 weeks gestation and has Hb A1C = 9.0% Treatment options for DM? 44
November 09, 2013 Type 2 DM • Despite increased use of oral hypoglycemics, most women still receive insulin • Starting dose = 0.7 – 1.0 units/kg/day g / g/ y • Thus is weight = 70 kg = 50 ‐ 70 total units per day • Key point = this is an approximation to start, much biological variation Insulin preparations Insulin preparations 45
November 09, 2013 Regimen Options • Long acting + rapid acting** – Glarganine (daily) – Humolog (with meals) • Intermediate acting + rapid – NPH (twice daily) – Humolog (with meals) Regimen Options Long acting + rapid acting 1/3 1/3 breakfast ½ Rapid 1/3 lunch Acting Total Daily Insulin Dose ½ Long 1/3 dinner Acting Regimen Option Intermediate acting + rapid acting 2/3 NPH 2/3 NPH 2/3 in AM 1/3 Rapid acting Total Daily Insulin Dose ½ NPH 1/3 in PM ½ Rapid acting 46
November 09, 2013 Regimen Options Management Pearls • If doing well pre ‐ pregnancy, don’t change schedule • Don’t change from Rapid Acting to Regular • Don’t give Regular at lunchtime • May need to change from long acting to intermediate acting – “Flat profile” in pregnancy may be undesirable when variations in basal insulin are likely Management Pearls • Ask/listen to patient for input on changes • Keep it simple, make changes based on patterns • Try to change one insulin and one dose at a time • Avoid hypoglycemia A id h l i • When control is poor, it is often the diet • DM compliance is proportional to how complex/difficult/burdensome the health provider makes insulin therapy 47
November 09, 2013 Case • Ms. Jones is G 4 P 3 here for 1 st prenatal care visit ‐ referred from family practice physician who confirmed pregnancy She has confirmed pregnancy. She has history of T2 diabetes but not on treatment. She is 12 weeks gestation and has Hb A1C = 9.0% Treatment options for DM? Glyburide • Second ‐ generation sulfonylurea that binds to pancreatic ‐ cell receptors to increase insulin secretion as well as increasing peripheral insulin • Brand names: Micronase, DiaBeta, Glynase • Onset of action = 30 minutes • Time to peak response = 2 ‐ 3 hours • Maximim daily dose = 20 mg (some reccomendations allow up to 30 mg/day) Glyburide and GDM • Langer et al. (NEJM) – RCT insulin vs. glybuide – Sample size = 404 – Similar improvements glycemia, LGA, macrosomia Similar improvements glycemia, LGA, macrosomia – 4% “failure rate” glybuide • Subsequent studies suggest failure rates 15 ‐ 20% – Risk factors failure = morbid obesity and fasting values > 110 ‐ 115 mg/dL 48
November 09, 2013 Glyburide vs. Metformin • Two RCT’s in GDM – Glybuide vs. Metformin – Combined sample size > 900 subjects – No difference major perinatal outcomes No difference major perinatal outcomes • However, 35 ‐ 46% of women on metformin required insulin • No safety issues noted metformin or glyburide Role Oral Hypoglycemics • Glyburide for GDM – Choose optimal candidates – Due to compliance issues may tolerate “risk of failure” and supplement insulin prn failure and supplement insulin prn • Extrapolated for T2DM – No large, high quality trials – Unknown risks/benefits Management Pearls • If a women is “stable” on metformin or glyburide and becomes pregnancy, reasonable to continue • Recognize “higher” failure rate with T2DM and g g unknown risks/benefits – Imperfect control and need for supplemental insulin may be better than no control – If have to add multiple dose insulin with oral agents, may be better to convert 49
November 09, 2013 Management of Chronic Hypertension, Renal Disease and Other Co ‐ Morbidities in the Diabetic Gravida Baha Sibai, M.D. Professor, Division of Maternal ‐ Fetal Medicine 50
November 09, 2013 Management of Chronic Hypertension, Renal Disease and other co ‐ morbidities in Diabetic Pregnancy Baha M. Sibai, MD Baha M. Sibai, MD Professor Director, Maternal Fetal Medicine Fellowship Department of Obstetrics, Gynecology & Reproductive Sciences Management of CHTN and medical co ‐ morbidities in diabetic Pregnancy Learning Objectives 1. To discuss the impact of preexisting medical conditions on pregnancy outcome in DM. 2. To discuss the effects of pregnancy on preexisting medical conditions in association with DM 3. To describe a step ‐ wise management plan for management of diabetic pregnancy in association with medical co ‐ morbidities White Classification for DM White Classification for DM Class Criteria Onset ≥ 20 yr or duration < 10yr B C Onset 10 -19 yr or duration 10-19yr (no vascular disease) Onset < 10 or duration ≥ 20 yr or retinopathy or HTN only ≥ 20 D D O t < 10 d ti ti th HTN l Nephropathy ( ≥ 500mg proteinuria at < 20 wk) F H Arteriosclerotic heart disease : ischemia, MI R Proliferative retinopathy T History of renal transplant 51
November 09, 2013 End Organ Damage in DM Target Target ‐ Organ Damage in DM Organ Damage in DM • Heart • Retinopathy – Non ‐ proliferative – Ischemia /MI – Proliferative – Angina: stable or unstable – Heart failure / LV • Neuropathy hypertrophy – Gastroparesis / / • Nephropathy peripheral – Incipient: micro ‐ albuminuria – Overt: 0.3 ‐ 3.0 g / 24 hr – Severe: > 3 g /24 hr – ESRD: CR >2.3 mg/dl Management of Co Management of Co ‐ morbidities morbidities in Diabetic in Diabetic Pregnancy Pregnancy • Current medications / • Evaluation prior to response to RX conception/first visit – Insulin, antihypertensives, – Glucose control (Hgb A1C) cardiac drugs – Presence of HTN, BP control – Other: Statins, thyroid Ot e Stat s, t y o d – Nephropathy medications – Retinopathy • Outcome in previous – Hyperlipidemia pregnancies – Myocardial ischemia – Preeclampsia, PTD, FGR, – Renal transplant, dialysis Perinatal death – Maternal complications 52
November 09, 2013 Factors Associated with Adverse Pregnancy Factors Associated with Adverse Pregnancy Outcome in DM Outcome in DM • Pre ‐ eclampsia • Pyelonephritis • Polyhydramnios • Poor Compliance P C li • Poor Management: – Poor control of glucose – Poor control of BP – Poor response to complications CHTN in pregestational DM CHTN in pregestational DM • Most common co ‐ morbidity ( 10 ‐ 40%) – Advanced age in type 2 – Obesity in type 2 – Increases rate of adverse outcome • BP and proteinuria will increase in pregnancy – Frequent adjustment of BP medications – More than one drug may be needed – DX of preeclampsia is difficult • Development of new onset SXs • Onset of Pulmonary edema • Change in platelets/ liver enzymes Pregnancy outcome in CHTN, DM & combined Variable Control Chronic HTN DM Both n=522,377 n=5560 n=3718 n=433 0.3 0.8 0.8 2.2 IUFD 2.7 2 7 28 7 28.7 9.5 9 5 31.7 31 7 Preeclampsia P l i 10.1 18.3 9.7 18.2 SGA 2.2 2.6 8.1 6.0 LGA 1.1 1.0 2.5 0.5 Shoulder dystocia 0.8 2.0 1.4 1.9 Placental abruptio Keenan E. et al. Am J Obstet Gynecol. 2012 Oct 53
November 09, 2013 Chronic HTN, DM, or Combined Pregnancy Outcomes 40 35 30 Chronic HTN 25 e Incidenc DM 20 BOTH 15 10 5 0 IUFD (per 1,000) <32 wk <37 wk preterm delivery Keenan E. et al. Am J Obstet Gynecol. 2012 Oct Preeclampsia in DM ± vascular disease 35 29% 30 26% 25 22% 20 20 18% 15 10 5 0 No hypertension or Proteinuria only Hypertension only Both hypertension proteinuria and proteinuria Sibai BM. et al. Am J Obstet Gynecol. 2000 Feb Target BP of 130/80 mm Hg in DM Target BP of 130/80 mm Hg in DM JNC Report , ADA, NKF JNC Report , ADA, NKF • Reduces macro & micro ‐ vascular complications – Retinopathy – Nephropathy – Ischemic heart disease Ischemic heart disease • In microalbuminuria, it reduces – Preeclampsia – PTD 54
November 09, 2013 Antihypertensive Drugs to Use in Antihypertensive Drugs to Use in Pregnancy Pregnancy Drug Usual dose( m g) Maxim um dose Labetalol 2 0 0 x 2 / d 2 4 0 0 Chlorothiazide 1 2 .5 -2 5 / d 2 5 Nifedipine ( LA) Nif di i ( LA) 1 0 -3 0 / d 1 0 3 0 / d 1 2 0 1 2 0 Nicardipine ( SR) 6 0 -1 2 0 / d 2 4 0 Metroprolol ( XL) 5 0 -1 0 0 / d 2 0 0 Hydralazine 1 0 -2 5 x 4 / d 3 0 0 Furosem ide 2 0 x 2 / d 8 0 Carvedilol B. Sibai, MD ACE Inhibitors ACE Inhibitors / ARBs in Pregnancy / ARBs in Pregnancy Usually safe prior to 16 wks Usually safe prior to 16 wks • Fetal Anomalies (? 1 st Trimester) • FGR • Oligohydramnios • Fetal deformations F t l d f ti • Neonatal renal dysfunction • Neonatal renal failure Diabetic Retinopathy in Pregnancy Diabetic Retinopathy in Pregnancy Dx Dx and Management and Management • Non ‐ proliferative – Mild: microaneurysms + dot hemorrhages – Severe: cotton ‐ wool spots, edema • Proliferative – New blood vessels in retina – Vitreous hemorrhage, retinal detachment i h h i l d h • Retinal digital imaging – First visit and 28 wk – 16 ‐ 20 wk if abnormal – If proliferative / macular edema: monthly • Laser Photocoagulation – Proliferative & macular edema 55
November 09, 2013 Diabetic Nephropathy Diabetic Nephropathy • Incipient: albumin 30 ‐ 300mg/24 hr • Overt: – Protein > 300 mg/24hr at ≤ 13 wks – Protein 300 ‐ 500 mg/24hr at < 20 wks Protein 300 ‐ 500 mg/24hr at < 20 wks • Prevalence of 5 ‐ 10% – Due to increased Type 2 • With or without HTN – Various stages of renal function – With or without retinopathy Renal Function changes in Diabetic Nephropathy Renal Function changes in Diabetic Nephropathy • GFR: limited change, ↑ in 33% • Proteinuria – 24/46 (58%) ↑ > 1g/24 from 1 st → 3 rd T – 25/46 (56%) > 3g/24h • Mild renal dysfunction (Cr <1.4; protein <3g/24h)* – Minimal impact on long ‐ term function • Moderate ‐ severe nephropathy (Cr >1.4)* – ESRD /dialysis during or after pregnancy – 45% accelerated, irreversible decline in function * Outcomes influenced by glycemic control, HTN, preeclampsia Pregnancy in Diabetic Nephropathy Pregnancy in Diabetic Nephropathy Factors associated with poor outcome Factors associated with poor outcome • Cr ≥ 1.4 mg/dl (124 µmol/L) • Proteinuria > 3g/24h • Hgb < 8g/dl • Chronic HTN > 5 yrs • Chronic HTN > 5 yrs • Left ventricular dysfunction by ECHO • Ischemic changes on ECG • Unstable angina in pregnancy • Poor compliance with insulin/antihypertensives Sibai, BM. Nephropathy in Diabetic Pregnancy 56
November 09, 2013 Pregnancy outcomes in Diabetic Pregnancy outcomes in Diabetic Nephropathy (%) Nephropathy (%) Kitzmiller Bagg Carr Reece Gordon Khoury Rosenn Sibai n=26 n=24 n=43 n=31 n=45 N=60 n=61 n=58 Pre ‐ Pre 15 15 33 33 35 35 35 35 53 53 40 40 51 51 36 36 eclampsia PTB < 35 wk 31 * 46 21 ** 23 * 16 * 15 ** 25 * 36 IUGR 21 ‐‐ 19 19 11 12 11 11 Perinatal 89 100 91 94 100 95 94 98 Survival *PTB <34 wk **PTB <32 wk Neonatal outcome in presence or absence of proteinuria Outcomes Proteinuria Proteinuria Present (n=86) Absent (n=376) No. % No. % Delivery at <37 wk Delivery at <37 wk. 50 50 58 58 125 125 33 33 Delivery at <35 wk. 25 29 50 13 Birth weight <10 th % 12 15 10 3 Birth weight >90 th % 12 15 147 40 Birth weight >4000g 3 4 68 18 NICU 56 70 166 46 Perinatal Death 3 4 8 2 Sibai BM. et al. Am J Obstet Gynecol. 2000 Feb Management of Diabetic Nephropathy Management of Diabetic Nephropathy Maternal Maternal • Glycemic Control • Monthly CBC, CMP – Hg A1c at 1 st visit starting at 24 wks – Self BG monitoring • Massive edema, – Multiple insulin proteinuria, ↓ albumin injections/pump injections/pump – Furosemide + albumin F id lb i • Hypertension Control – Lovenox prophylaxis – Goal of 130/80 mm Hg – CCB /Beta blockers – Diuretics 57
November 09, 2013 Management of Diabetic Nephropathy Management of Diabetic Nephropathy Fetal testing, timing of delivery Fetal testing, timing of delivery • Serial U/S for growth, AFI • UA Doppler if FGR • NST / BPP at 28 wks – Repeat 1 ‐ 2x/wk as needed Repeat 1 2x/wk as needed – Immediate if acute change • Delivery at 34 ‐ 37 wks or earlier – Obstetric complications – Medical complications Diabetic coronary Diabetic coronary heart disease heart disease in Pregnancy in Pregnancy • Maternal death: 8/24 (33%) • Ischemia / MI – Ischemia/MI prior preg (0/11) – Hyperlipidemia – MI in pregnancy : 8/13 (62%) – Young, Type 1 • Existence of non ‐ cardiac • Heart failure/ LV / organ damage organ damage hypertrophy – Renal – Type 2 – Retinal – Old and high parity – Hyperlipidemia – Obese – Hypertension – Hypertensive – Family HX Diabetic Heart Diabetic Heart Disease in Pregnancy isease in Pregnancy Evaluation & Counseling Evaluation & Counseling • Prior to pregnancy/ 1 st visit – ECG, ECHO, stress test – Nuclear medicine cardiac imaging – Cardiac Cath, Angiography – Medications – Stent – Defibrillator • Counseling – Recent MI, unstable angina : Avoid pregnancy – MI or unstable angina < 20 wk: Discuss options – Discuss complications – Need for prolonged hospitalization 58
November 09, 2013 Diabetic heart disease in Pregnancy Diabetic heart disease in Pregnancy Management & Delivery Management & Delivery • Management • Delivery – Stable angina: – Hemodynamic stable • Beta ‐ blockers – Induction at term • LDA – Myocardial infarction • Nitrates – Delay for at least 2 weeks – Unstable angina: – Invasive monitoring • Stent – ? C/S or operative delivery • Coronary bypass surgery – Close postpartum monitoring – Myocardial infarction : – Morphine – Heparin/ TPA/ Aspirin – IV nitro, – Coronary bypass – Admit to CCU – Heart failure – Dysrhythmia Diabetes with hyperlipidemia /atherosclerosis Diabetes with hyperlipidemia /atherosclerosis Effects of Pravastatin Effects of Pravastatin • Antithrombotic action • Interferes with coagulation cascade – Downregulation of TF – Upregulation of thrombodulin – Reduce thrombin/ factor Va generation Reduce thrombin/ factor Va generation • Inhibits platelet activation – Downregulation of cyclooxygenase1 – Upregulation of NO synthase • Cholesterol lowering action : plaque stabilization Diabetic patients with co Diabetic patients with co- -morbidites morbidites Maternal – Maternal – Fetal Management Fetal Management • Liberal Hospitalization – Evaluation & RX of complications • Frequent prenatal visits • Aggressive control of BS / BP gg • Monitor organ function(serial) • U/S for fetal growth – 28 wks & every 3 wks • NST / BPP at 28 wks • Delivery at ≤ 37 wks 59
November 09, 2013 Diabetic patients with co Diabetic patients with co- -morbidites morbidites Recommendations Recommendations • Pregestational diabetics should be evaluated for TOD • Good pregnancy outcome is achieved by: • Tight BP and glucose control • Compliance with medications and visits • Management of target organ damage g g g g • Proper M ‐ F surveillance • Timely delivery at a tertiary center • In women with HTN, the goal BP is < 130/80 mmHg • Women with ESRD / CAD should be counseled against pregnancy • Diabetics with comorbidities require multidisciplinary management 60
November 09, 2013 Fetal Imaging and Antenatal Testing for the Diabetic Gravida Eleazer Soto, M.D. Assistant Professor, Division of Maternal ‐ Fetal Medicine 61
November 09, 2013 Fetal Imaging and Antenatal Testing for Pregnant Women with Diabetes Eleazar Soto M.D Assistant Professor Division of Maternal Fetal ‐ Medicine University of Texas Health Science Center at Houston (UTHealth Medical School) Congenital anomalies in Diabetic patients • Most important cause of perinatal death in pregnancies complicated by type 1 and type 2 Diabetes Mellitus 2 Di b M lli • Congenital anomalies accounts for 30 ‐ 50% of all perinatal mortality. Reece EA, et al. Obstet Gynaecol Surv 1986; 41:325 ‐ 335. Roberts AB. et al. N Z Med J 1990; 103:211 ‐ 213. Hawthorne G. et al BMJ 1997; 315:279 ‐ 281. Congenital anomalies in Diabetic patients • There are no specific abnormalities associated with increasing maternal hyperglycemia • The degree of maternal hyperglycemia appears • The degree of maternal hyperglycemia appears to have a greater influence on the number of organ systems rather than on the specificity of the organ involved Schaefer ‐ Graf UM, et al. Am J Obstet Gynecol 2000; 182:313 ‐ 320. 62
November 09, 2013 Frequency of Congenital Anomalies in Infants of Diabetic Mothers Author Number of Patients % Mills et al. 25/279 9.0 Greene et al Greene et al. 35/451 35/451 7.7 7 7 Steel and Duncan et al. 12/239 7.8 Fuhrmann et al. 22/292 7.5 Simpson et al. 9/106 8.5 Albert et al. 29/289 10 Congenital anomalies in Diabetic patients • The prevalence of major congenital anomalies: – 46 per 1000 births in women with diabetes – 48/1000 births for type 1 diabetes (4.8%) – 43/1000 births for type 2 diabetes (4.3%) • Rate of anomalies in the general population (1 ‐ 2%) • 6 ‐ 30% may have multiple anomalies in pregestational Diabetes Mellitus MacIntosh MCM et al. BMJ 2006; 333:177 Reece EA, et al. Am J Perinatol 1998; 15:549 Interesting Fact: • Rate of anomalies reported in New Zealand; – Type 1: 5.9% / Type 2: 4.4% – Gestational Diabetes 1.4% • Women with Gestational Diabetes were then • Women with Gestational Diabetes were then reclassified after postnatal glucose tolerance – The congenital abnormality rate for those women later reclassified as having unrecognized type 2 diabetes was 4.6%, whereas in the remaining women with gestational diabetes , the rate had fallen to 0.9%. Farrell et al. Diabet Med 2002; 19:322 ‐ 326 63
November 09, 2013 Lancet, 1978 Vo 312 (8097) p 956 ‐ 9 Hb A Hb A 1c above 8.5 had above 8 5 had 22.4% anomalies N Engl J Med. 1981 May 28;304(22):1331 ‐ 4 The risk of major or minor congenital anomaly according to peri ‐ conceptional hemoglobin A 1c congenital anomaly 40 35 30 25 Absolut risk (%, 95% CI) of 20 20 15 14 15 12 10 8 10 7 6 5 4 5 3 3 2 0 5.5 6.2 6.9 7.6 8.3 9.0 9.7 10.4 11.1 11.8 12.5 13.2 >13.9 Periconceptial A1C (%) Jensen DM. et al. Diabetes Care. 2009 Jun;32(6):1046 ‐ 8 Guerin A. et al. Diabetes Care 2007;30:1920–1925 Combined frequnecy of major congenital anomaly and spontaneous abortion according to the HbA1c during the first trimester of pregnancy 80 SAB (percent) 70 60 50 50 Major malformation or S 40 30 20 10 0 <9.3 9.4 ‐ 11 11.1 ‐ 12.7 >12.7 Hemoglobin A1c (percent) Greene MF, et al, Teratology 1989; 39:225 64
November 09, 2013 Diabetes Teratogenesis Somatomedin Genetic inhibition HLA subtypes Ketone Free oxygen Hyperglycemia body excess radical excess Multifactorial Color atlas of clinical embryology. Moore 1994 Complete AV canal defect 65
November 09, 2013 Ventricular septal defect (VSD) Hutzel Hospital, Detroit. Type II DM at 20 weeks with The ventricular septum and free septum and free walls appear thicker than usual Wayne State University, Hutzel Hospital, Detroit Medical Center Cranial Signs of Neural Tube Defect Hutzel Hospital, Detroit. 66
November 09, 2013 Neural Tube Defect Hutzel Hospital, Detroit. Dhaulakhandi et al. Fetal Diagn Ther. 2010;28(2):72-78. Anencephaly Hutzel Hospital, Detroit. 67
November 09, 2013 Holoprosencephaly Hutzel Hospital, Detroit. Holoprosencephaly Hutzel Hospital, Detroit. Unilateral Renal Agenesis Twining P. Genitourinary Malformations. In: Diagnostic Imaging of Fetal Anomalies 1 st Edition 2003 68
November 09, 2013 Caudal regression Hutzel Hospital, Detroit CONGENITAL MALFORMATIONS IN INFANTS OF DIABETIC MOTHERS Cardiovascular system Transposition of the great vessels, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation, single umbilical artery, hypoplastic left ventricle, cardiomegaly Central nervous system Anencephaly, open neural tube defects, holoprosencephaly, absent corpus callosum, Arnold ‐ Chiari anomaly, schizencephaly, microcephaly, macrocephaly, agenesis of olfactory tracts, hydrocephaly olfactory tracts, hydrocephaly Gastrointestinal system Pyloric stenosis, duodenal atresia, microcolon, anorectal atresia, omphalo ‐ enteric cyst/fistula, hernias Urogenital system Renal agenesis, renal cysts, hydronephrosis, duplication of ureter, ureterocele, uterine agenesis, micropenis, hypospadias, cryptorchidism, hypoplastic testes, ambiguous genitalia Musculoskeletal system Caudal dysgenesis, craniosynostosis, costovertebral anomalies, limb reduction, club foot, contractures, polysyndactyly Other Cleft palate J Obstet Gynaecol Can. 2007 Nov;29(11):927 ‐ 44 CONGENITAL MALFORMATIONS IN INFANTS OF DIABETIC MOTHERS Cardiovascular system 2 to 34 per 1000 births Central nervous system 5 per 1000 births Urogenital system 2 to 32 per 1000 births Gastrointestinal system 1 to 5 per 1000 births Musculoskeletal system 2 to 20 per 1000 births J Obstet Gynaecol Can. 2007 Nov;29(11):927 ‐ 44 69
November 09, 2013 Late developing anomalies Duodenal atresia Hutzel Hospital, Detroit. Echogenic Kidneys 70
November 09, 2013 Nuchal translucency: 11–13+6 weeks scan Nicolaides KH. The 11-13+ 6 weeks scan; Fetal medicine foundation; 2004 Hutzel Hospital, Detroit. Reference range of fetal NT with CRL 99 th centile is about 3.5 mm throughout gestational range Nicolaides KH. The 11-13+ 6 weeks scan; Fetal medicine foundation; 2004 71
November 09, 2013 First trimester and diabetes • Increasing nuchal thickness confers greater risk of all major types of CHD, even among euploid fetuses • At least 25 ‐ 50%of fetuses with CHD have increased nuchal translucency • Nuchal translucency appears to predict the presence of congenital heart disease better than most traditional risk factors Hyett J et al. BMJ. 1999;318(7176):81 Makridymas G. et al. Am J Obstet Gynecol. 2003;189(5):1330 Bahado ‐ Singh R. Am J Obstet Gynecol. 2005;192(5):1357 When should we attempt to screen for anomalies and do an anatomical survey? • First trimester nuchal thickness measurement: 11 ‐ 13 6/7 weeks measurement: 11 ‐ 13 6/7 weeks • BMI <30: 18 ‐ 22 weeks • BMI>30: >20 ‐ 22 weeks • 12169 low ‐ risk pregnant women and 130 women with pre ‐ existing diabetes • 8% of anomalies in Diabetes group vs 1.4% in 8% f li i i b 1 4% i low risk group • Detection rate of congenital anomalies for diabetic women was significantly lower than that for the general population within the same institution (30% vs. 73%) 72
November 09, 2013 Majority of women who had repeat ultrasound scans still had unsatisfactory image quality Wong SF et al. Ultrasound Obstet Gynecol. 2002 Feb;19(2):171 ‐ 6 Importance of the antenatal detection of major congenital anomalies • Allows discussion of the options of termination of pregnancy, • In selected cases, fetal surgery. • Preparation for optimal management at and following delivery. Should all women with pregestational diabetes need pregestational diabetes need fetal echocardiography? 73
November 09, 2013 Should all women with pregestational diabetes need fetal echocardiography? • Increased nuchal translucency in the first trimester • Suspected cardiac anomaly during a comprehensive fetal anatomic survey ultrasound h i f t l t i lt d • When the cardiac views are restricted by increased body fat and confirmation of normal cardiac structure cannot be made. • Four chamber with LVOT and RVOT may be cost ‐ effective NICE guidance on diabetes in pregnancy, clinical guideline 63. London, March 2008 Fetal growth and Diabetes Fetal growth and Diabetes • 4,000 to 4,500 g • birth weight above the 90th percentile for population and sex ‐ specific growth curves sex specific growth curves Wayne State University/ Hutzel Hospital. Detroit Medical Center 74
November 09, 2013 Diabetes, growth abnormalities and ultrasound • Macrosomia affects up to 50% of all diabetic pregnancies. – Shoulder dystocia – Erb’s palsy – Cesarean section • Range of error of ultrasound is about 15% • Accuracy of estimated fetal weight is worse in women with diabetes and for macrosomic babies • No difference in the proportion of women with type 1 or type 2 diabetes with antenatal evidence of macrosomia Wong SF. Australian and NZJOBG 2001;41(4):429–32. BancerrafBR. AJOG1988;159:118–21 Diabetes in pregnancy: are we providing the best care? Findings of a national enquiry: CEMACH; 2007. How often should we do fetal growth assessments? • Starting at 28 weeks • Then around 32 ‐ 34, and 37 ‐ 38 wks Then around 32 34, and 37 38 wks Antepartum Fetal Surveillance Antepartum Fetal Surveillance 75
November 09, 2013 Chronic Fetal Intrauterine Hypoxia Acidosis Hypokalemia ‐ Placental Cardiac Dysrhythmias Dysfunction Ketoacidosis preeclampsia Fetal Death or Stillbirth in Diabetes Antepartum Fetal Surveillance • The goal of antepartum fetal testing is to prevent fetal death • Several techniques, NST, BPP, modified BPP, and Umbilical artery Doppler • Each method has been independently found to be predictive of fetal compromise in high risk pregnancy groups. However, whether the tests are equally predictive in pregnancies with diabetes is questionable ACOG, Practice B ulletin #9. 1999 Antepartum Fetal Surveillance • Stillbirth and perinatal mortality rates per 1000 births compared with the general population were 26.8 and 31.8 versus 5.7 and 8.5. and 8.5. • Stillbirths have been observed most often after the 36th week of pregnancy in patients with vascular disease, poor glycemic control, hydramnios, fetal macrosomia, or preeclampsia 76
November 09, 2013 Stillbirth rates in women with and without Gestational Diabetes 25 Stillbirth rates in women with GDM (per 10000 20 ongoing pregnancies) Stillbirth rates in women Stillbirth rates in women Deaths per 10000 15 without GDM (per 10000 ongoing pregnancies) 10 5 0.0 38 39 36 37 40 41 42 Gestational age (weeks) Rosentein MG. et al. Am J Obstet Gynecol. 2012 Apr;206(4):309.e1 ‐ 7 BPP and diabetes • A normal test result, is usually thought to be reassuring of fetal well ‐ being • Limitations Johnson JM. Obstet Gynecol 1988; 72:841 ‐ 846 Dicker D. Am J Obstet Gynecol 1988; 159:800 ‐ 804. What are the limitations of BPP in diabetic pregnancies? 77
November 09, 2013 Polyhydramnios is often associated with Diabetes (poorly controlled) Rise in maternal glucose levels is known to stimulate fetal breathing movements Umbilical artery • Conflicting results regarding UA artery RI and PI and maternal glycemia • No association between umbilical artery y resistance and HbA1c levels • If diabetic vasculopathy is present , placental 24 function may be affected, thereby increasing the risk for fetal growth restriction 78
November 09, 2013 Gestational Diabetes and antenatal testing • Women with gestational diabetes and diet control (well controlled A1) do not require antenatal testing • Women with gestational diabetes poorly controlled with diet that requires therapy (i.e insulin or glyburide) require antenatal testing. When to start • 34 weeks of gestation (10 point BPP) • Testing can be started earlier if any co ‐ morbidity is present (i.e. IUGR, CHTN) How often • Clinical judgment • Once or twice weekly ACOG practice bulletin 9, reaffirmed 2009 ACOG ACOG practice bulletin 9, reaffirmed 2009 79
November 09, 2013 Obstet Gynecol. 2009 Mar;113(3):687 ‐ 701 NICE guidance on diabetes in pregnancy, clinical guideline 63. London, March 2008 Summary • Congenital anomalies is the first cause of perinatal death and morbidity among women with diabetes mellitus • The rate of fetal anomalies is 4 ‐ 5% • Hemoglobin A1C may be of values for counseling H l bi A1C b f l f li and screening patients during the first trimester • Cardiovascular and CNS anomalies are the most common anomalies • Nuchal Translucency measurement between 11 ‐ 13 6/7 weeks is recommended to assess the risk of Cardiovascular disease. 80
November 09, 2013 Summary • Comprehensive anatomy survey 18 ‐ 22 weeks • Selective Fetal echocardiogram • Growth scan every 4 weeks starting at 28 Growth scan every 4 weeks starting at 28 weeks • Weekly antenatal testing after 34 weeks – 10 point BPP (NST and BPP) – Earlier if additional complications or indications are present Th Thank you k 81
November 09, 2013 Umbilical artery and DM • UA PI is higher in Diabetic pregnancies than uncomplicated pregnancies. • No association between umbilical artery resistance and HbA1c levels resistance and HbA1c levels • Conflicting results regarding UA artery RI and PI and maternal glycemia • If diabetic vasculopathy is present , placental function may be affected, thereby increasing the risk for fetal growth restriction 82
November 09, 2013 Lemon and Banana (spina bifida) • Abnormal anterior • Frontal bone scalloping curvature cerebellar • Seen in 1% normal hemispheres fetuses • False ‐ positive extremely rare Late developing anomalies • Some anomalies do not become manifest until late in pregnancy: • Duodenal atresia. The stomach may not increase in size and the duodenum may not y dilate until well after 20 weeks. • infantile polycystic kidney disease, where the kidneys may not become enlarged or ‘echogenic’ in appearance until after the 20th week Why BPP is controversial in diabetic pregnancies? • A rise in maternal glucose levels is known to stimulate fetal breathing movements, contributing to a positive score for one of the components of the BPP. • Maternal diabetes is often associated with increased amniotic fluid, again a positive score in the BPP. • two of the five tests of fetal well ‐ being are influenced positively simply by having diabetes in pregnancy Dicker D, et al. Am J Obstet Gynecol 1988; 159:800 ‐ 804. 83
November 09, 2013 Timing and Mode of Delivery for the Diabetic Gravida Sean Blackwell, M.D. Chair, Department of Obstetrics, Gynecology and Reproductive Sciences 84
November 09, 2013 Timing and Mode of Delivery for the Diabetic Gravida Sean C. Blackwell, M.D. Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences Director, Larry C. Gilstrap M.D. Center for Perinatal and Women’s Health Research Assistant Dean for Healthcare Quality in Perinatal Medicine and Women's Health University of Texas Medical School at Houston (UTHealth) Medical School Sean.blackwell@uth.tmc.edu Objectives • To discuss the rationale for medically ‐ indicated delivery < 39 wks for women with DM in pregnancy. • To review the risks and benefits of medically y indicated delivery < 39 wks for women with DM in pregnancy. • To review the risks and indications for cesarean delivery in women with DM in pregnancy. Why Timed Delivery? • Women with pre ‐ gestational DM – Effort for “tight” glycemic control – Multiple visits, tests, imaging – Achieve 37 wks Achieve 37 wks • Getting to term GESTATION is “VICTORY” for many DM women 85
November 09, 2013 Why Timed Delivery? • Balancing the risks of : Neonatal M&M (delivery 37 ‐ 38 wks) Vs. Continued Pregnancy (delivery >= 39 wks) Potential maternal and newborn Potential maternal and fetal Vs. consequences of early term birth consequences of continued pregnancy Maternal Morbidity & Mortality (preeclampsia, poor glycemic control ) Fetal Morbidity & Mortality ( (Stillbirth, Uteroplacental insufficiency, shoulder dystocia) ff ) Neonatal Morbidity & Mortality (Immaturity Related) Maternal Morbidity & Mortality (Prolonged/Failed induction, Cesarean delivery) 37 wks 38 wks 39 wks Gestational Age 86
November 09, 2013 Timing of Indicated Late Preterm and Early Term Birth Workshop and Early Term Birth Workshop Co-sponsored by o Eunice Kennedy Shriver National Institute of Child Health and Human Development and o Society for Maternal Fetal Medicine February 7-8, 2011 San Francisco, CA 87
November 09, 2013 ACOG committee opinion no. 560: Medically indicated late ‐ preterm and early ‐ term deliveries. • The neonatal risks of late preterm (34 0/7 ‐ 36 6/7 weeks of gestation) and early ‐ term (37 0/7 ‐ 38 6/7 weeks of gestation) births are well established. • However, there are a number of maternal, fetal, and placental complications in which either a late ‐ preterm or early ‐ term p p y delivery is warranted. • The timing of delivery in such cases must balance the maternal and newborn risks of late ‐ preterm and early ‐ term delivery with the risks of further continuation of pregnancy. Decisions regarding timing of delivery must be individualized. • Amniocentesis for the determination of fetal lung maturity in well ‐ dated pregnancies generally should not be used to guide the timing of delivery. NICHD Work Shop • Pre ‐ gestational – Well controlled, compliant, no co ‐ morbidity 39–40 wks – Co ‐ morbidity, including FGR, follow particular condition – With preexisting vascular disease, consider 37 ‐ 39 wks – Poorly controlled even after optimization, including hospitalization, consider < 39 wks consider < 39 wks • Gestational – Well controlled on lifestyle changes, deliver 39 ‐ 40 wks – Well controlled on medication, deliver 39–40 wks – Poorly controlled or non ‐ compliant deliver 37 wks, individualize before 37 wk (consider intensive control) – Co ‐ morbidity, including FGR, follow particular condition Bottom Line: Timing Pregestational DM + medication requiring GDM • Medically indicated < 39 wks – Co morbidities (HTN, renal Dz) – IUGR – Poorly controlled even after optimization • No data comparing 37 vs 38 wks for medically ‐ indicated timed delivery • Limited value amniocentesis for FLM 88
November 09, 2013 Bottom Line: Timing “39 week Rule “ • Delivery prior to 39 weeks in this woman whose pregnancy is complicated diabetes is medically i di indicated. d • As the maternal fetal medicine physician caring/consulting in this case I recommend timed delivery at 38 wks. Mode of Delivery: Diabetes Centers report 50 ‐ 75% CD for pre ‐ gestational DM AJP 2010 Why is CD rate so high? • High labor induction rates – Term and PTB • Prior cesarean and low TOLAC • Increasing obesity and morbid obesity • Multiple co ‐ morbidities • Risk SD with suspected macrosomia 89
November 09, 2013 Shoulder dystocia and BW ACOG Shoulder dystocia PB 1997 Suspected macrosomia • Planned cesarean delivery to prevent shoulder dystocia may be considered for suspected fetal macrosomia with EFW > 4,500 grams – Implication GDM and pre ‐ gestational DM • Key issues ‐ – Literature states clinical and U/S EFW similar accuracy – EFW error up to 20% if EFW > 4000 grams – Labor induction doesn’t decrease SD risk – Informed consent Bottom Line: Cesarean • GDM – 30 ‐ 40 % overall CD rate • Pre ‐ gestational DM – 50 ‐ 60 % overall CD rate • High % with prior CD and low TOLAC rate • Of women without prior CD, very high induction rates (40 ‐ 50%) • High % obesity (60 ‐ 75% with BMI > 30 kg/m 2 ) 90
November 09, 2013 Intrapartum and Postpartum Management of Diabetes Janice Whitty, M.D. Professor, Division of Maternal ‐ Fetal Medicine 91
November 09, 2013 Intrapartum and Postpartum Management of Diabetes Janice E. Whitty, MD Professor, Maternal ‐ Fetal Medicine Department of Obstetrics, Gynecology & Reproductive Sciences The University of Texas Health Science Center at Houston Department Safety Officer Medical Director, Labor & Delivery – Lyndon B. Johnson Hospital Disclosure Statement I do not have relevant financial I do not have relevant financial relationships with commercial interests related to the content of this presentation. Learning Objectives Examine guidelines and recommendations for intrapartum and postpartum for intrapartum and postpartum management of women with gestational and pre ‐ gestational diabetes. 92
November 09, 2013 Intrapartum Management Gestational Diabetes & Type II DM Co ‐ Morbidities • Obese • CHTN • Preeclampsia • Utero ‐ placental insufficiency • Intrapartum Hemorrhage • Infection • Thromboembolic disease • Failed regional anesthesia, intubation Intrapartum Management On Admission • CBC, BMP, T&S • Anesthesia consult • EFW/EFM • Consider fetal macrosomia and shoulder dystocia d f l d h ld d • TED Hose, SCDs • Strict I&O • NPO • IV access Intrapartum Key Therapeutic Goal: Avoid Maternal Hyperglycemia! Reduced: d d – Fetal Acidemia – Neonatal hypoglycemia Avoid hypoglycemia as well 93
November 09, 2013 Intrapartum Fetal Acidemia Fetus � Glucose � Insulin � Metabolic Rate � Oxygen Consumption � Arterial Oxygen � Fetal Acidemia Intrapartum Fetal Hypoxemia • Hyperglycemia • Ketoacidosis • Preeclampsia • Maternal Vasculopathy • All can reduce placental blood flow Neonatal Hypoglycemia • > 50% of macrosomic newborns • Glucose < 35 ‐ 40 mg/dl in first 15 hrs. of life • Rapid drop in glucose after cord clamping • Maternal glucose control last half of gestation l l l l h lf f • Maternal glycemic control during L&D • � Cord free insulin and C ‐ peptide • Exaggerated pancreatic response to glucose loading 94
November 09, 2013 Obese Newborn Potential Role of Fetal Exposure to Maternal Type II Diabetes Impaired glucose Insulin tolerance Resistance Genetic Beta cell Factors Diabetes dysfunction Environmental Factors Diabetes during pregnancy Intrapartum Maternal Glucose Targets: • 70 ‐ 110 mg/dl (3.9 ‐ 6.1 mmol/L) • Type I, Type 2 and GDM yp yp • Obtained from observational data primary involving outcome in Type 1 DM • Glucose levels >180 mg/dl will result in neonatal hypoglycemia. ACOG 2005 Garber Endocrine Practice 2004 95
November 09, 2013 Intrapartum Gestational Diabetes Diet Controlled (GDMA1) • Rarely require insulin in labor y q • Measure glucose on admission • Start glucose infusion D5LR@125 ml/hr • Check glucose every 4 hours • If glucose >120 mg/dl start insulin infusion Planed Cesarean IDDM • Give PM insulin or PO meds • Decrease dose of PM long acting insulin • NPO after 12 MN • Start IV Dextrose @ 125 ml/hr. • If CS delayed give 1/3 of AM intermediate insulin or cover with sliding scale • Monitor glucose intra op and cover • Monitor glucose q2h post op IDDM/GDM A2 Intrapartum Glucose Management • Bedtime usual dose of intermediate ‐ acting insulin or agent • Hold AM insulin dose • Begin intravenous infusion of normal saline • Check glucose hourly • Check glucose hourly • Active labor or glucose < 70 mg/dL • Start 5% Dextrose 100–150 cc/hr. (2.5 mg/kg/min) to achieve a glucose level of 100 mg/dL. • Start Regular insulin IV @ 1.25 U/h if glucose levels exceed 100 mg/dL. Data from Coustan DR. Delivery: timing, mode, and management. In: Reece EA, Coustan DR, Gabbe SG, editors. Diabetes in women: adolescence, pregnancy, and menopause. 3rd ed 96
November 09, 2013 Titrate Insulin Infusion Intrapartum Glucose Management Post Partum Pre ‐ gestational � Insulin Requirements risk for hypoglycemia • Monitor glucose every 2 ‐ 4 hr. • Diabetic diet • Insulin 1/2 ‐ 1/3 end of pregnancy dose • Type 2 may not need insulin for 24 ‐ 48 hrs • Encourage breastfeeding • Need 500 additional Kcal (CHO 100 g, protein 20 g) 97
November 09, 2013 … • …. Postpartum GDM • Most will not need hypoglycemic therapy • Check FBS • FBS < 126 d/c home on regular diet • If FBS ≥ 126 DM ‐ refer for therapy f f f h • Encourage breastfeeding, exercise and weight loss (tip NIH App LactMed for drugs in BF) • Counsel re risk of overt DM, need for f/u • 2 hr. GTT at 6 weeks 98
November 09, 2013 Risk of DM after GDM • Up to 30% will have DM or impaired GT • Sevenfold lifetime risk of DM • FH, race and obesity increase the risk , y • LGA children of women with GDM have increased risk of DM and 50% have evidence of the metabolic syndrome • Obesity is increased in children of GDM Diagnostic Criteria for Diabetes Mellitus, Impaired Fasting Glucose, and Impaired Glucose Tolerance. IMPAIRED FASTING IMPAIRED TEST DIABETES GLUCOSE GLUCOSE TOLERANCE Fasting glucose gg Fasting glucose ≥ 126 Fasting glucose = 100-125 gg gg Not applicable pp 75-g 2-hr. oral glucose tolerance test Fasting glucose ≥ 126 Fasting glucose = 100-126 2-hr glucose = 140- or 199 2-hr glucose ≥ 200 Gestational Diabetes Postpartum Follow ‐ up • Content of slide 99
November 09, 2013 Contraception IDDM • Barrier preferred • IUD no increased infection • Combined low dose OC may increase TE and MI restrict use to those without vascular or other risk factors • Depo ‐ Provera (DMPA) deterioration in CHO metabolism, TG & HDL, TC and LDL unchanged • Progestin only preferred Kjos 1990 Contraception GDM • Prospective randomized study • 230 women recent H/O GDM • Randomized to low dose combined vs. progestin only R d i d t l d bi d ti l • No significant difference in progression to DM • OC no adverse effect on TC, LDL, HDL or TG Summary • Tight glucose in the control last half of pregnancy and Intrapartum may prevent fetal acidemia and neonatal hypoglycemia • Women who require insulin or oral hypoglycemic • Women who require insulin or oral hypoglycemic therapy should be managed with glucose and insulin drips in labor • Glucose should be 70 – 110 mg/dl • Women who have GDMA1 rarely need insulin in labor 100
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