Diabetes & Pregnancy By: Carolyn Connors

Diabetics and Pregnancy Euglycemia is very important! Decreases likelihood of: Miscarriage Congenital anomalies Macrosomia Fetal death Neonatal morbidity

Diabetic Embryopathy Occurs in 6-7th weeks GA Maternal Hyperglycemia leads to vascular disruption and yolk sac failure Increased spontaneous abortions Major malformations

Fetal Effects Pathophysiology – Maternal hyperglycemia Fetal hyperglycemia Premature maturation of pancreatic islets Hypertrophy of beta cells Hyperinsulinemia

Hypertrophy of Beta Cells

Fetal Hypoxemia Chronic fetal hyperinsulinemia Increased activity hepatic enzymes Increased glycogen and lipid storage Increased metabolic rates Oxygen consumption increased

Fetal Hypoxemia Stimulates erythropoietin polycythemia Promotes catecholamine production HTN Cardiac hypertrophy Contributes 20-30% stillbirth rate in poorly controlled diabetics

Neonatal Effects Congenital anomalies – Accounts for 50% of perinatal deaths of infants of diabetic mothers (IDM) Relative risk increased 7% with IDM over general population

Congenital Anomalies Two-thirds involve CVS or CNS Anencephaly and Spina bifida 20x more common in IDM GU, GI, MSK defects increased

Congenital Anomalies Left Colon Syndrome - Transient inability to pass meconium Resolves spontaneously Condition unique to IDM’s

Congential Anomalies Caudal Regression Syndrome – 200x more common in IDM Incomplete development of sacrum/lumbar region Distal spinal cord disrupted Neurologic impairment varied Leg deformities

Premature Delivery Increased Iatrogenic premature delivery Maternal preeclampsia Increased spontaneous premature labour Associated with poor glycemic control High rates of UTI’s

Perinatal Asphyxia Defined to include: Fetal heart rate abnormalities during labor Low Apgar scores Intrauterine death

Perinatal Asphyxia Correlated with: Maternal vascular disease Eg: nephropathy Hyperglycemia during labor Prematurity

Increased Fetal Growth Mostly during 3rd trimester Disproportionate growth Insulin sensitive tissue eg. Liver, muscle, cardiac muscle, subcutaneous fat Head circumference normal Increased risk of hyperbilirubemia, hypoglycemia, acidosis

Macrosomia

Macrosomia Birth weight > 90th percentile or > 4000g Predisposes to birth injury Eg: Shoulder Dystocia Brachial plexus injury Clavicular/Humeral Fractures Perinatal asphyxia

Shoulder Dystocia

Shoulder Dystocia Occurs in 1/3 IDM > 4000g Disproportionate growth contributes C-Section often recommended if fetal weight > 4300g

Intrauterine Growth Restriction Maternal Vasculopathy Preclampsia Congenital Anomalies Very strict BG control

Respiratory Distress Syndrome Causes amoung IDM: Delayed maturation of surfactant synthesis Hypertrophic cardiomyopathy Retained lung fluid (TTN) Increased rates of c-section

Hypertrophic Cardiomyopathy Fetal hyperinsulinemia increases fat/glycogen deposit in cardiac muscle Thickening interventricular septum 30-50% IDM with hypertrophy on Echo Obstructed left ventricular outflow 5-10% symptomatic

Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy Transient condition Echo normalizes 6-12 months Symptomatic infants recover after 2-3 weeks supportive care

Hypoglycemia BG levels < 2.2 Occurs within hours of birth Increased risk with both LGA and SGA infants

Polycythemia 13-33% IDM’s Hct should be measured 12hrs after birth Can lead to Hyperviscosity Syndrome Renal vein thrombosis Vascular sludging, ischemia, infarction of vital organs

Polycythemia

Hyperbilirubinemia Associated with: Poor maternal glycemic control Polycythemia Macrosomic infants prematurity

Neurodevelopmental Outcome Few studies available which adequately control confounders Maternal ketones Poorer psychomotor development Elevated HbA1c levels during pregnancy Poorer intellectual performance

Neurodevelopmental Outcomes Developmental Delay IUGR Congenital malformations

Risk of Developing Diabetes Type 1 DM: Some genetic component: Offspring – 6% Siblings – 5% Identical twins – 30% (general population – 0.4%)

Risk of Developing Diabetes Type 2 DM: Much larger genetic component Abnormal intrauterine metabolic environment IDM – 45% Prediabetic – 8.6% Nondiabetic – 1.4%

Impaired Glucose Tolerance Obesity Increased BMI noted in offspring of diabetic mothers (ages 5-19 yrs) Birth weight not indicative Impaired Glucose Tolerance

Prepregnancy Counselling Required to decrease complications in known diabetics: Macrosomia: 63% (10%) C-Section: 56% (20%) Preterm delivery: 42% (12%) Preeclampsia: 18% (6%) Congenital Malformations: 5% (3%) Perinatal Mortality: 3% (<1%)

Complete History/Physical Exam Duration/Type of DM Acute complications Chronic complications Glucose management Physical activity Medication Obs/Gyne History

Laboratory Investigations Urinalysis Treat asymptomatic bacteriuria Baseline renal function Total protein, serum Cr, CrCl Thyroid Function TSH, Free T4

Comprehensive eye exam Within 12 months prior to pregnancy Within 1st trimester Followed closely up to 1 year postpartum

Assessing Glycemic Control HgbA1C: mean blood glucose concentration over preceding 6 - 8 weeks HgbA1A – In Pregnancy: Mean BG concentration over 4 – 6 weeks Life span of RBC shortened due to increased production

Hemoglobin A1C Measured every 4-6 weeks Goal < 6.1 prior to d/c contraception Associated with lowest rate of adverse pregnancy outcome Spontaneous abortion Congenital malformation Perinatal death

Assessing Glycemic Control Glucose monitoring: Pregnancy associated with exaggerated rebound from hypoglycemia Urine Ketones: Type 1 DM with illness or BG > 11.1 DKA associated with high fetal mortality rate Ketonemia may have adverse developmental effects.

Target Blood Glucose Values Fasting glucose < 5.2 1 hr postprandial glucose < 7.7 2 hr postprandial glucose < 6.6 Qhs < 5.9 Strict glycemic control decreases adverse fetal outcomes

Hazards of Strict Glycemic Control Hypoglycemia – does not appear to be teratogenic in humans Extremely strict control (BG < 4.8) can cause small-for-gestational age infants

Hazards of Strict Glycemic Control 2. Diabetic Retinopathy – Related to degree of baseline retinopathy Magnitude of reduction of chronic hyperglycemia Mediated by closure of small retinal blood vessels that were narrowed but patent Frequent retinal evaluation recommended in high risk women

Retinopathy Comprehensive eye exam Within 12 months prior to pregnancy Within 1st trimester Followed closely up to 1 year postpartum

Nutritional Therapy Achieve euglycemia Prevent ketosis Provide adequate weight gain Contribute to fetal well-being

Caloric Requirements Increase 300 kcal/day in pregnancy Based on BMI: 30-40 kcal/kg/day – BMI < 22 30-35 kcal/kg/day – BMI 22-27 24 kcal/kg/day – BMI 27-29 12-15 kcal/kg/day – BMI > 30

Maternal obesity can cause: Excessive fetal growth Increase glucose tolerance Caloric restriction may be useful treatment

Oral Anti-hyperglycemic Agents Sulfonylureas – can cross the placenta causing fetal hyperinsulinemia: Macrosomia Neonatal hypoglycemia

Oral Anti-hyperglycemic Agents Glyburide – High protein binding so placental passage low Several studies have not shown harmful effects

Oral Anti-Hyperglycemic Agents Metformin and Thiazolindiones – Minimal information available

Recommendations Oral anti-hyperglycemics not recommended in pregnancy Some question as to usage in non-compliant patients on individualized basis Insulin - patients unable to obtain euglycemia through diet alone

Insulin Therapy Type 2 DM: Insulin during preconception period Obtain adequate HgbA1C Avoid excessive weight gain Moderate low-impact exercise

Insulin Therapy Rapid Acting Insulin (Lispro/Aspart) Acceptable safety profiles Minimal transfer across the placenta No evidence teratogenesis Note: Compared to Regular Insulin Improves postprandial BG Decreases risk hypoglycemia

Insulin Therapy Longer Acting Insulin: NPH recommended Glargine: high affinity for IGF-1 receptor Risk of macrosmia

Intrapartum Management Latent phase – insulin to maintain BG 3.9-5.0 Active Phase – insulin resistance rapidly decreases BG check hourly Avoid boluses of glucose Increases risk of neonatal hypoglycemia Fetal hypoxia Fetal/neonatal acidosis

Postpartum Management Postpartum - insulin requirements drop sharply Short ½ lives of placental growth hormone and placental lactogen Insulin doses readjusted 24-72 hrs Note: Breast-feeding patients should remain on insulin

The End!