Diabetes in Pregnancy

1. Diabetes in Pregnancy

2. Pregnancy may be complicated by diabetes in two distinct forms: • Gestational diabetes mellitus (GDM) is defined as glucose intolerance of varying severity with onset or first recognition during pregnancy. This subset constitutes 90% of women with pregnancies complicated by diabetes. The most important perinatal concern in this group is macrosomia with resulting birth trauma. More than 50% women ultimately develop diabetes in the ensuing 20 years and this is linked with obesity. • Pre-gestational diabetes is diabetes that antedates pregnancy. Pregnancies which are complicated by pre-gestational diabetes, type-1 or type-2, carry an additional risk to both mother and fetus beyond the effects on fetal growth and development in mid and late pregnancy.

3. Classification • Pregestational diabetes: A lady with known diabetes who conceives while on treatment with diet, oral hypoglycemic agents or insulin. Type 1 DM, Type 2 DM, Secondary DM • Gestational diabetes mellitus is defined as glucose intolerance of variable degree with onset or first recognition during pregnancy. Some patients with fasting hyperglycemia detected early in pregnancy may be missed cases of diabetes that predated pregnancy. Women found early in pregnancy to have gestational diabetes are a high-risk subgroup.

4. Risk Factors for gestational diabetes screening • Strong family history of diabetes • Women who have given birth to large infants (>4 kg; 8 lbs 13 oz) • History of recurrent fetal loss • Persistent glycosuria • Age > 25 years • Past history of glucose intolerance or diabetes in a previous pregnancy

5. Risk Factors for gestational diabetes screening 7. Obesity; overweight women (>15% of non-pregnant ideal body weight) 8. Ethnic group with a high prevalence of diabetes (e.g. Pima Indians, Asians, Hispanic) 9. History of stillbirth, unexplained neonatal death, congenital malformations, prematurity. 10. History of pre-eclampsia or polyhydraminos 11. Chronic hypertension 12. Recurrent severe moniliasis or urinary tract infection 13. History of traumatic delivery with an associated neurological disorder in the infant

6. Pathophysiology: • Caused by placental production of human placental lactogen (HPL) and progesterone. • Other hormones that may contribute include prolactin and cortisol.

7. Pathophysiology-cont: • Early in pregnancy, relatively higher levels of estrogen enhance insulin sensitivity. • As placenta develops, estrogen decreases as HPL and progesterone rise, resulting in increased insulin resistance at the end organs. • Insulin resistance is most marked in the third trimester at which time GDM most often occurs.

8. Pathophysiology-cont: Insulin • is the major fetal growth hormone . • produces excessive fetal growth particularly in fat, the most insulin-sensitive tissue.

9. Growth Abnormalities(1)Two Extremes Of Growth Abn:

10. Whom to screen? Risk stratification • Low risk: no screening • Average risk: at 24-28 weeks • High risk: as soon as possible Screening is ideally initiated between the 24th and 28th weeks of pregnancy or earlier if any of the risk factors are present.

11. Low risk for GDM • Age <25 years • Weight normal before pregnancy • Member of an ethnic group with a low prevalence of GDM • No known diabetes in first-degree relatives • No history of abnormal glucose tolerance • No history of poor obstetric outcome

12. High risk for GDM Intermediate risk for GDM Must exhibit one risk factor from the list in slide 5. • Marked obesity • Prior GDM • Glycosuria • Strong family history • Ethnic group with high diabetes prevalence

13. Screening test • Glucose Challenge Test (GCT): An excellent screening test for gestational diabetes is the measurement of plasma glucose 1 hour after ingesting 50 g of glucose. A plasma glucose level obtained one hour after a 50 g glucose load administered at any time of the day without regard to the time since the last meal, has become a well validated and widely applied screening procedure for women between 24 and 28 weeks of gestation. Using a cut-off value > 140 mg/dl identifies 80% women with GDM Using a cut-off value > 130 mg/dl identifies 90% women with GDM Women with elevated GCT values require a diagnostic oral glucose tolerance test

14. Screening test Oral Glucose Tolerance Test (OGTT): Measurement of plasma glucose after ingesting 100 g of glucose. > 2values must be abnormal; for at least 3 days prior to the test, the patient should have an unrestricted diet and unlimited physical activity. The patient should fast for 8 hours before the test. The CC criteria detects 54% more women with GDM than the NDDG criteria Classification: and diagnosis of diabetes mellitus and other categories of glucose intolerance: National Diabetes Data Group. Diabetes 1979;28:1039–1057 Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol. 1982;144:768-73.

15. Urine monitoring Urine glucose monitoring is not useful in gestational diabetes mellitus Urine ketone monitoring may be useful in detecting insufficient caloric or carbohydrate intake in women treated with calorie restriction

16. Effects of GDM on the fetus • Congenital abnormalities • Neonatal hypoglycemia • Macrosmia (big baby syndrome > 4 Kg or >8 lb 13 oz) • Jaundice • Polycythemia / hyperviscosity syndrome • Hypocalcemia, hypomagnesemia • Birth trauma (due to macrosmia and shoulder dystocia) • Prematurity • Hyaline membrane disease • Apnea and bradycardia The risk of fetal anomalies is not increased in GDM patients. However, the risks of unexplained still births (during the last 4-8 weeks of gestation) are similar to pre-gestational diabetes.

17. Effects of GDM on neonates Respiratory distress Hypoglycemia Hypocalcemia Hyperbilirubinemia Cardiac Hypertrophy Long term effects on cognitive development

18. Macrosomic infant Macrosomia (large for gestational age or big baby syndrome) (birth weight >90% percentile for gestational age) Macrosomia is a result of persistent maternal hyperglycemia leading to fetal hyperglycemia and prolonged fetal hyperinsulinism. This stimulates excessive somatic growth mediated by insulin-like growth factors (IGFs). Macrosomia affects all organs except the brain.

20. Infant of a Diabetic Mother with Sacral Agenesis • Cardiovascular anomalies: ASD, VSD • Skeletal anomalies: sacral agenesis • CNS anomalies • Genitourinary anomalies: renal agenesis, polycystic kidneys

21. Congenital abnormalities due to GDM • Cardiac (most common): transposition of great vessels, Ventricular septal defect, Atrialseptal defect • Central nervous system (7.2%): spina bifida, Anencephaly, hydrocephalus • Skeletal: cleft lip/palate, caudal regression syndrome • Genitourinary tract: ureteric duplication • Gastrointestinal: anorectalatresia • Renal agenesis, Duplex ureters, Cystic Kidney • Situsinversus Poor glycemic control at time of conception: risk factor

22. Caudal regression syndrome (abnormal development of lower spine)

23. Caudal regression syndrome

24. Effects of GDM on the mother • Pre-eclampsia: affects 10-25% of all pregnant women with GDM • Infections: high incidence of chorioamnionitis and postpartum endometritis • Postpartum bleeding: high incidence caused by exaggerated uterine distension • Cesarian section more common due to fetal macrosmia and cephalo-pelvic disproportion • Weight gain • Hypertension • Miscarriages • Third trimester fetal deaths • Long term risk of type-2 diabetes mellitus

25. Effect of pregnancy on diabetes • More insulin is necessary to achieve metabolic control • Progression of retinopathy: esp. severe proliferative retinopathy • Progression of nephropathy: especially if renal failure + • Increased risk of Coronary artery disease, and a high risk of maternal death in post MI patients • Cardiomyopathy

26. Management: • The goal is to prevent adverse pregnancy outcomes. • A multidisciplinary approach is used. • Patient is seen every 1-2 wks until 36 wks gestation and then weekly. • Patient is asked to keep an accurate diary of their blood glucose concentration.

27. Dietary Therapy: • Refer to a dietitian • Recommend a complex, high fiber CHO diet • Avoid concentrated sweets

28. When Dietary Therapy Fails: • Insulin • Oral Hypoglycemic Agents: -Glyburide -Metformin

29. Insulin Regimen: • Pt should check their fasting glucose and a 1 hour or 2 hour postprandial glucose level after each meal, for a total of four determinations each day. • If the fasting value is > 95 mg/dL, or 1 hr value > 130-140 mg/dL or 2 hr value > 120 mg/dL, insulin therapy needs to be initiated.

30. Patient educationCornerstone in GDM management • Instruct mother about maternal and fetal complications • Medical Nutrition therapy • Glycemic monitoring: teach mother about self monitored blood glucose measurement and glycemic targets • Pre-conception counseling • Fetal monitoring: ultrasound • Planning on delivery • Long term risks

31. Vaginal delivery: preferred Cesarean section only for routine obstetric indication GDM alone is not an indication ! > 4.5 Kg fetus: Cesarean delivery may reduce the likelihood of brachial plexus injury in the infant Unfavorable condition of the cervix is a problem Maintain euglycemia during labor Maternal hyperglycemia in labor: fetal hyperinsulinemia and worsen fetal acidosis Maintain sugars: 80-120 mg/dl (capillary: 70-110mg/dl ) Feed patient the routine GDM diet Maintain basal glucose requirements Monitor sugars 1-4 hrly intervals during labour Give insulin only if blood sugar >120 mg/dl Management of labor and delivery

32. Timing of delivery Small risk of late intra-uterine death even with good glycemic control Delivery usually at 38 weeks Beyond 38 weeks, increased risk of intrauterine death without an increase in RDS

33. Delivery: Early delivery may be indicated for: • women with poor glycemic control • pregnancies complicated by fetal abnormalities Otherwise, pregnancies are allowed to go to term.

34. Intrapartum: The goal is to maintain normoglycemia in order to prevent neonatal hypoglycemia. • Check patient’s glucose q1-2 hours. • Start insulin drip to maintain a glucose level of between 80 - 110 mg/dL. • Observe infant closely for hypoglycemia, hypocalcemia, and hyperbilirubinemia after birth.

35. Glycemic management during labour Later stages of labor: start dextrose to maintain basal nutritional requirements: 150-200 ml/hr of 5% dextrose Elective Cesarean section: check fasting blood sugar; if within target range no insulin is needed; start dextrose drip Continue hourly self monitored blood glucose Post delivery keep patients on dextrose-normal saline till fed No insulin unless sugars more than normal ( not GDM targets ! )

36. Hypoglycemia: 50 % of macrosomic infants 5–15 % optimally controlled GDM Starts when the cord is clamped Exaggerated insulin release secondary to pancreatic ß-cell hyperplasia Increased risk: blood glucose during labor and delivery exceeds 90 mg/dl Immediate management of neonate Anticipate and treat hypoglycemia in the infant

37. Management of neonate • Hypoglycemia <40 mg/dl • Encourage early breast feeding • If symptomatic give a bolus of 2- 4 ml/kg, IV, 10% dextrose • Check after 30 minutes, start feeding • IV dextrose : 6-8 mg/kg/min infusion • Check for calcium, if seizure/irritability/RDS • Examine infant for other congenital abnormalities

38. Postpartum Care: After delivery: • Measure blood glucose. -fasting blood glucose concentrations should be <105 mg/dL and one hour postprandial concentrations should be < 140 mg/dL. • Administer one half of the pre-delivery dose before starting regular food intake.

39. Postpartum Care-cont: Follow up: • If the pt’s postpartum GTT is normal, she should be re-evaluated at a minimum of 3 years interval with a fasting glucose. • All pts should be encouraged to exercise and lose wt. • All pts should be evaluated for glucose intolerance or DM before a subsequent pregnancy.

40. Self monitored blood glucose (SBMG) • 4 times/day minimum, fasting and 1 to 2 hours after start of meals • Maintain log book • Use a memory meter • Calibrate the glucometer frequently

41. Post partum follow up • Check blood sugars before discharge • Breast feeding: helps in weight loss • Lifestyle modification: exercise, weight reduction • Oral glucose tolerance test at 6-12 weeks postpartum: classify patients into normal/impaired glucose tolerance and diabetes • Preconception counseling for next pregnancy Increased risk of cardiovascular disease, future diabetes and dyslipidemia

42. Long term risk: offspring • Increased risk of obesity and abnormal glucose tolerance due to changes in fetal islet cell function • Encourage breast feeding: less chance of obesity in later life • Lifestyle modification

43. Conclusion • Gestational diabetes is a common problem in worldwide • Risk stratification and screening is essential in all pregnant women, particularly those from ethnicities with increased risk • Tight glycemic targets are required for optimal maternal and fetal outcome • Patient education is essential to meet targets • Long term follow up of the mother and baby is essential

44. Courtesy: MSNBC News Services Jan. 24, 2005 17 pound baby born to Brazilian diabetic mother