Diabetes in Pregnancy

1. Diabetes in Pregnancy Dr Thomas Paul MD DM (Endo) Dr. Mathew John MD DM(Endo) Department of Endocrinology Christian Medical College Vellore

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. Magnitude of problem: GDM • GDM varies worldwide and among different racial and ethnic groups within a country. • Variability is partly because of the different criteria and screening regimens • Prevalence : India: 0.56% -6% (Ramachandran A et al 1994; Hill et al., 2005) USA: increased from 2.1–4.1% in the period 1994 to 2002 with significant increases in all racial/ethnic groups (Dabelea et al., 2005). Native Americans, Asians, Hispanics, African-American, Aboriginal women are at higher risk (Ferrara, 2007). Ramachandran A, Snehalatha C, Shymala P, Vijay V, Viswanathan M. Prevalence of diabetes in pregnant women--a study from southern India. Diabetes Res Clin Pract. 1994;25:71-74. Hill JC, Krisgnaveni GV, Annamma I, Leary SD, Fall CH. Glucose tolerance in pregnancy in South India: relationships to neonatal anthropometry. Acta Obstet Gynecol Scand. 2005;84:159-65 Dabelea, D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ, Hamman RF, McDuffie RS. Increasing Prevalence of Gestational Diabetes Mellitus (GDM) Over Time and by Birth Cohort. Diabetes Care 2005;28:579-584 Ferrara A: Increasing prevalence of gestational diabetes mellitus. Diabetes Care 2007;30:S141-S146

5. 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

6. 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

7. 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.

8. 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

9. 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

10. All Indian women and women of Indian origin should be screened for gestational diabetes mellitus as they belong to a high risk ethnicity

11. 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

12. 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.

13. 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

14. 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.

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

16. 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.

17. 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

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

19. Caudal regression syndrome

20. 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

21. 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

22. 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

23. Glycemic control targets • Tight glycemic control can reduce fetal risk. But, stringent glycemic control puts the mother at increased risk of hypoglycemic events and the fetus at risk of being small-for-gestational age. • American Diabetes Association Recommendations: These are venous plasma targets, not glucometer targets

24. Why these tight glycemic targets? Prospective study in type-1 patients with pregnancy

25. 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

26. Medical Nutrition and Exercise therapy • provide necessary nutrients for mother and fetus to ensure adequate gestational weight gain • control glucose levels • prevent starvation ketosis • aerobic exercise, exercise that does not stress the trunk

27. Medical nutrition therapy • Approximately 30 kcal/kg of ideal body weight • > 40-45% should be carbohydrates • 6-7 meals daily (3 meals, 3-4 snacks). Bed time snack to prevent ketosis • Calories guided by fetal well being/maternal weight gain/blood sugars/ ketones • Energy requirements during the first 6 months of lactation require an additional 200 calories above the pregnancy meal plan

28. Insulin in GDM • Insulin used if fasting blood glucose >105 mg/dl or 1 hr postprandial blood glucose >120 mg / dl on a diet • Use basal bolus regime or pre-mixed insulin • Short acting insulins (e.g. Lispro and Aspart) can be used to achieve postprandial control • Long acting insulins (Glargine and Determir) are NOT licensed in pregnancy • Insulin requirements increase by 50% from 20-24 weeks to 30-32 weeks, after which insulin needs often stabilize.

29. Oral Hypoglycemic agents Glyburide is a clinically effective alternative to insulin in GDM (Langer et al. 2000) Metformin may be effective in GDM (Ratner et al., 2008; Coustan, 2007) Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med. 2000;343:1134-8 Ratner RE, Christophl CA, Metzger BE, Dabalea D, Bennett PH, Pi-Sunyer X, Fowler S, Kahn SE, Diabetes Prevention Program Research Group. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab. 2008;93:4774-9 Coustan DR Pharmacological management of gestational diabetes: an overview. Diabetes Care. 2007;30 Suppl 2:S206-8.

30. Preconception counseling All women with pre-existing type-1 or type-2 diabetes, when planning on pregnancy, should receive pre-conception counseling so that they understand the importance of achieving near-normal blood glucose before conception to reduce the risk of congenital malformations and spontaneous abortions. • Assess maternal and fetal risk • Mother should learn self-administration of insulin and regular monitoring of blood glucose. • Target: HbA1c < 7% • Emphasize diet and exercise • Folic acid supplementation: 5 mg/day • Ensure no transmissible diseases: HBsAg, HIV, rubella • Try and achieve normal body weight: diet/exercise • Stop drugs: oral hypoglycemic drugs, ACE inhibitors, beta blockers and potentially teratogenic drugs

31. Clinical parameters checked at each visit • Medications • Pre-pregnancy weight • Weight gain • Edema • Pallor • Thyroid enlargement • Blood pressure • Fundal height

32. Laboratory parameters to be monitored at each visit • Hemoglobin • Blood Sugar • HbA1C (first trimester only) • Urine microscopy and albumin • Thyroid function (if goiter present)

33. Fetal monitoring • Baseline ultrasound : fetal size • Ultrasound evaluation of neural tube defects and other congenital malformations should begin by 15-21 weeks of • At 18-22 weeks: fetal anatomic survey, major malformations • At 20-22 weeks: fetal echocardiogram for cardiac defects • At 26 weeks onwards: ultrasound to evaluate fetal growth and amniotic fluid volume • Third trimester: Fetal surveillance to reduce risk of still birth: include non-stress test, biophysical profile, maternal monitoring of fetal activity, frequent USG for accelerated growth • abdominal: head circumference

34. 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

35. Management of labor and delivery • Vaginal delivery: preferred • Cesarian 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

36. Glycemic management during labour • Later stages of labour: start dextrose to maintain basal nutritional requirements: 150-200 ml/hr of 5% dextrose • Elective Cesarian 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 ! )

37. 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

38. Immediate management of neonate • 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 Anticipate and treat hypoglycemia in the infant

39. 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

40. 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

41. 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

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