Disclosure Diabetes in Pregnancy I have no conflicts of interest to disclose Jennifer Krupp, MD Maternal Fetal Medicine St. Marys Hospital/SSM Health Madison, WI Objectives Classification of Diabetes Classifications of Diabetes Diagnosis of Maternal & Fetal Morbidity Preconception Counseling Antepartum, Intrapartum and Post Partum Management Pregestational Diabetes Mellitus Type 1 Type 2 A1 diet controlled A2 requires medication Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Chronic Autoimmune disease Natural History 3 stages 1. Pancreatic beta-cell injury mediated by humoral and cellular activity 2. Pre-diabetic stage progressive islet cell destruction in the pancreas 3. Overt diabetes stage -inadequate insulin production by the islet cell-depleted pancreas leads to severe metabolic consequences. Natural History 5 stages 1. Tissue insulin-resistance insulin resistance in muscle and adipose tissue leads to altered tissue glucose uptake and hyperglycemia 2. Glucotoxicity hyperglycemia directly inhibits glucose uptake into target cells by down regulating the glucose transporter system. 3. Lipotoxicity insulin resistance leads to increased lipolysis in the visceral fat. 4. Impaired glucose tolerance fasting hyperglycemia present, glucotoxicity and lipotoxicity are ongoing. 5. Overt diabetes blood glucose elevated in fasting and postprandial state. Meet diagnosis criteria by ADA 1
Mellitus Arises from significant insulin resistance In many cases, preclinical Type 2 DM is unmasked by hormonal stress of pregnancy Complicates 2.5% of pregnancies (135,000 cases annually) Maternal Glucose Regulation Hypoglycemia between meals and at night due to fetus drawing glucose from maternal bloodstream Progressive insulin resistance requires increase in insulin production to 2x prepregnant levels Failure to augment pancreatic insulin output maternal & fetal hyperglycemia Maternal Morbidity Maternal Morbidity Relative risk of morbidity is proportional to the duration and severity of disease Retinopathy Nephropathy Cardiovascular Complications Chronic HTN Preeclampsia Heart Disease Retinopathy Leading cause of blindness ages 24-64yo Present in 100% women with DM > 25 years Pregnancy accelerates these changes Prospective study -50% of patients experienced deterioration during pregnancy all had partial regression PP returned to prepregnancystate by 6 months PP Screen prior to pregnancy & 1st trimester Minimal disease reexamine 1-2 x during pregnancy Significant disease reexamine monthly Maternal Morbidity Maternal Morbidity Nephropathy 20-30% of patients with Type 1 or 2 DM develop nephropathy over time Pregnancy does not alter time course of renal disease Progression is related to duration of diabetes & glycemic control Normal pregnancy increase in renal blood flow and GFR by 30-50% 3rd trimester MAP and PVR rise, women with diabetic microvascular disease marked decrease of renal function, worsened HTN & preeclampsia Increased BP & rapid decrease creatinine clearance PTD to avoid renal failure and stroke End-Stage Renal Disease Prognosis of pregnancy in women with ESRD is poor 60% premature delivery 20% end in live births 40% with severe IUGR Difficult to manage increased vascular volume of pregnancy with dialysis IUGR Best strategy is to undergo renal transplant prior to pregnancy 2
Maternal Morbidity Maternal Morbidity Cardiovascular Complications - Chronic HTN BP >140/90 before 20 weeks In 10-20% pregnant women with diabetes In 40% of those with preexisting renal or retinal vascular disease Suspect if BP>130/80 before 3rd trimester Diagnosis strengthened by: Failure of mean BP to decrease in 2nd trimester Creatinine >1mg/dL Cardiovascular Complications- Preeclampsia Occurs 2-3 times more in women with pregestational diabetes Longer duration of DM increased risk of preeclampsia 30% of women with DM >20 years develop preeclampsia Assess renal function each trimester Maternal Morbidity Cardiovascular Complications Preclinical cardiomyopathy and autonomic neuropathy may be present in patient with DM Arteriosclerotic heart disease may be seen in women in their 40 s Pregnancy outcome is poor 50% maternal mortality 30% fetal loss rate Obtain cardiac history, ECG, Echo in patients >30 years old or have had DM >10 years Spontaneous Abortion Congenital Anomalies IUGR Fetal Obesity Birth Injury Abnormal Maternal Glucose Regulation and Fetal Morbidity Elevated PP BG fetal hyperglycemia & hyperinsulinemia increased storage of excessive nutrients macrosomia Increased catabolism of extra nutrients uses energy depleted fetal oxygen stores fetal hypoxia Fetal hypoxia increased release of adrenal catecholamines HTN, cardiac remodeling & hypertrophy, increased Hct due to stimulation of erythropoietin & red cell hyperplasia Congenital Anomalies General pop. risk of major birth defect 1-2% Hgb A1C - preconception 3.4% rate of anomaly if HgbA1C <8.5% 22.4% rate of anomaly if HgbA1C >8.5% Majority of anomalies involve CNS Cardiovascular system 3
Intrauterine Growth Restriction In preconception diabetic pregnancies due to underlying maternal vascular disease Asymmetric IUGR in patients with vasculopathy (retinal, renal or CHTN) Brittle control frequent episodes of ketosis and hypoglycemia preeclampsia & poor fetal growth Poor placental function/blood flow IUGR Fetal Overgrowth (Macrosomia) Increased 3-fold in diabetic pregnancies Fetal macrosomia: EFW >4500g Skeletal growth unaffected Adipose accumulation in 3rd trimester Excessive and distributed in truncal region Fetal fat deposition occurs after 28 weeks Pathophysiology of Fetal Overgrowth Maternal Obesity Women with BMI >40 have 3 fold risk of having a fetus with macrosomia 50% increased risk of macrosomia when patient is >300 pounds Fetal birth weight correlates with 2nd & 3rd trimester postprandial blood glucose levels 2 hrpp <120mg/dL20% were macrosomic 2 hr PP 120-160mg/dL 35% were macrosomic Shoulder Dystocia Most injuries due to difficult vaginal delivery and shoulder dystocia Shoulder dystocia occurs in 0.3-0.5% of vaginal deliveries in normal pregnancy Brachial plexus injury Facial Nerve Injury Fetal weight > 4000 grams risk 5-7% Much higher risk if forceps or vacuum used Hypertrophic & Congestive Cardiomyopathy Prevalence 30% at birth; resolution by 1 year Cardiac dysfunction respiratory distress Often asymptomatic & unrecognized Echo hypercontractile, thickened myocardium with septal hypertrophy Pathogenesis is unclear Respiratory Distress Syndrome Neonates of diabetic moms are 20x more likely to develop RDS Distress may be due to decreased production of alveolar surfactant Fetal lung maturity occurs later in pregnancy with poor glycemic control 4
Preconception Counseling Preconception Counseling Goals: Decreases morbidity & mortality of mom & fetus Provide prognostic information, taking into account glycemic, cardiovascular, renal and eye status Provide advice re: risks & alternatives to medications the woman is taking Provide direct management to normalize preconception glucose levels & Hgb A1C Hypertension HTN in 20-30% of women who have had diabetes >10 years ACE inhibitors improve proteinuria & delay progression to renal failure in women with nephropathy ACE inhibitors decreased fetal renal blood flow oligohydramnios & fetal renal failure when used in 2nd or 3rd trimester Need to discontinue ACE during preconception period Diagnosis of Antidiabetic Oral Therapy Insulin Therapy Postpartum Management Diagnosis ACOG recommendations: Screening in general population at 24-28 weeks Option 1 50 gram 1-hour oral glucose tolerance test Cutoff 130 mg/dlor 140 mg/dl If >200 mg/dl, then no further testing 100 gram 3-hour oral glucose tolerance test Option 2 not supported by ACOG 75 gram 2-hour oral glucose tolerance test Cutoff Fasting 92; 1 hour 180; 2 hour 153 1 abnormal = GDM Diagnosis 3 hour GTT No comparative studies that show significant difference between the two ACOG states can use either one 2 abnormal values = GDM Diagnosis ACOG recommends early screening in high risk populations History of GDM in previous pregnancy Known impaired glucose metabolism BMI >30 These patients screened in 1st Trimester If negative, retest at 24-28 weeks gestation 5
Diabetes Screening and Diagnosis Treatment Management with Diet A1 GDM Management with Medication A2 GDM Oral antidiabetic agents Glyburide Metformin Insulin Therapy Fast acting Long acting American Diabetes Association 2018 Clinical Practice Recommendations First trimester maternal serum screening Level II fetal anatomy ultrasound at 20 weeks gestation Blood sugar monitoring A1GDM serial fetal growth ultrasounds every 4 weeks beginning at 28 weeks gestation A2GDM serial fetal growth ultrasounds every 4 weeks beginning at 28 weeks gestation Antenatal testing with NST beginning at 32 weeks gestation Delivery in 39th week of gestation Option of scheduled cesarean section if EFW > 4500 grams Pregestational Diabetes Baseline preeclampsia studies in 1st Trimester Hemoglobin A1c each trimester Serial fetal growth evaluation every 4 weeks beginning at 28 weeks gestation Fetal surveillance beginning at 32 weeks gestation NST Biophysical profile Delivery in the 39th week of gestation Option of cesarean section if EFW >4500 grams Intensive intrapartum insulin management Postpartum Management Screening 6 weeks postpartum Fasting blood sugar 75 gram 2-hour oral glucose tolerance test ADA recommends repeat testing at least every 3 years Pregestational Diabetes Insulin requirements decrease rapidly after delivery Should have plan for insulin dosage postpartum Breastfeeding Need to increase caloric intake 500kcal/day more than prepregnancy caloric intake Small snacks before and after breastfeeding 6