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Diabetes and Pregnancy. Dr Wong Pui Yee, Bonnie MBChB, MRCOG FHKAM(OG), FHKCOG Subspecialist in Fetal Maternal Medicine. 2 parts:. Preexisting DM and pregnancy Gestational diabetes. Preexisting diabetes in pregnancy. Type 1 DM ( IDDM) Type 2 DM (NIDDM). Preexisting DM in pregnancy.
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Diabetes and Pregnancy Dr Wong Pui Yee, Bonnie MBChB, MRCOG FHKAM(OG), FHKCOG Subspecialist in Fetal Maternal Medicine
2 parts: • Preexisting DM and pregnancy • Gestational diabetes
Preexisting diabetes in pregnancy • Type 1 DM ( IDDM) • Type 2 DM (NIDDM)
Preexisting DM in pregnancy Effect of pregnancy on pre-existing DM • Increase requirement for insulin doses • Nephropathy , autonomic neuropathy may deteriorate • Progress in diabetic retinopathy (2X) • Hypoglycemia • Diabetic ketoacidosis
Preexisting DM In Pregnancy Effect of preexisting DM on pregnancy • Maternal 1. increase risk of miscarriage 2. increase risk of preclampsia 3. increase risk of infection eg vaginal candidiasis, UTI, endometrial or wound infection 4. increase LSCS rate
Preexisting DM in Pregnancy (2) Fetal 1. increase risk of congenital abnormalities sacral agenesis, congenital heart disease, neural tube defects Hba1c levelRisk normal not increased <8% 5% >10% 25 %
Preexisting DM in Pregnancy 2. Perinatal mortality (excluding congenital abnormality ) 2 fold increased 3. Increase risk of sudden unexplained intrauterine fetal death.
Maternal: Increase insulin requirment’ Hypoglycemia Infection Ketoacidosis Deterioration in retinopathy’ Increased proteinuria+edema Miscarriage Polyhydramnio Shoulder dystocia Preeclampsia Increased caesarean rate Fetal: Congenital abnormalities Increased neonatal and perinatal mortality Macrosomia Late stillbirth Neonatal hypoglycemia Polycythemia jaundice Complications of pregnancy in pre-existing DM
Maternal hyperglycemia | Fetal hyperglycemia | Fetal pancreatic beta-cell hyperplasia | Fetal hyperinsulinaemia | Macrosomia,organomegaly, polycythaemia, hypoglycemia, RDS
Management Aim Achieve maternal near normoglycemic level to prevent adverse perinatal outcomes
Diet • Low-carbohydrate diet , high fibre with caloric restriction • Frequent small snacks may be needed between meals • Avoid starvation
Insulin • 3 pre-meal short acting insulin (actrapid) +/- intermediate-acting insulin (protophane) as it allows maximum flexibility • Target blood glucose: fasting < 5mmol/L 2 hr <7 mmol/L
Oral Hypoglycemic agents • Implicated as teratogeneic in animal studies esp first generation sulfonyureas • In humans, scattered case reports of congenital abnormality • Risk of congenital abnormality related to maternal glycemic control rather than mode of the anti-DM agents
Oral hypoglycemic agents • For Type 2 DM patients, to stop oral hypoglycemic agents and change to insulin Reassure that the risk of congenital abnormality due to drug is small
Oral hypoglycemic agents • Biguanides ( metformin) • Cat B drug • Commonly used in Polycystic Ovarian Disease (PCOD) to treat insulin resistance and normalize reproductive function • Not teratogeneic • Reduce first trimester miscarriage • 10X reduce gestational diabetes Glueck, Fertil Steril 2002 Reece, Curr Opin Endocrinol Diabetes, 2006 Hague, BMJ, 2003 Glueck, Human Reprod, 2004
Oral hypoglycemic agents Sulfonylureas • 1st generation drug increase risk of neonatal hypoglycemia • 2nd generation drug (Glyburide) no such effect and other morbidities . • Cat C drug • 4%-20% patients failed to achieve glucose control with maximum dose of drug • Increase risk of preeclampsia and need for phototherapy Langer, N Eng Med J , 2000 Kremer, Am J Obst Gynaecol, 2004 Chmait, J Perinatol ,2004 Langer, Am J Obst Gynaecol, 2005
Insulin Analogues • 1. rapid-acting insulin analogs (lispro) Cat B concerns about teratogenesis, antibodies formation, growth-promoting properties majority of evidence showed that it does not cross placenta, and has no adverse maternal or fetal effects
Insulin Analogues 2. Long acting analogs glargine Cat C drug Not well studied systemically
Monitoring • Regular home glucose monitoring with h’stix • Insulin may be need to be adjusted as gestation advances • Hba1c monitoring • Fetal monitoring with USG • Refer ophthamologist
Delivery • Timing and mode of delivery individualised • Intrapartum insulin infusion with glucose monitoring • no contraindication for Breast feeding either with insulin or oral hypoglycemic agents
Pre-conception Counselling • Allows for optimisation of diabetic control prior to conception, and assessment of the presence of complications like hypertension, nephropathy, and retinopathy • Should counsel that good control and lower hba1c lower the risk of congenital abnormalities and improve outcome • If necessary, proliferative retinopathy may be treated with photocoagulation prior to conception • Contraindications to pregnancy only :ischemic heart dx, untreated proliferative retinopathy, severe renal impairment(creatinine>250 mmol/L)
Gestational diabetes Definition Carbohydate intolerance of variable severity first recognised during the present pregnancy. This includes women with preexisting but previously unrecognised diabetes
Gestational diabetes No consensus for 4 decades!
Gestational diabetes • Should all pregnant women be screened or only those with risk factors? • Is it safe to screen all? • Which screening test and which diagnostic test are the most reliable? • Which cut-off values should we use? • What are the risk for mothers and babies and can treatment improve outcome? • What are the connection between gestational diabetes and type 2 DM? • Is it physiological or pathological ?
Gestational diabetes Screening and diagnosis In general, the test is performed btn 24-28 wk because at this point in gestation the diabetogenic effect of pregnancy is manifest and there is sufficient time remaining in pregnancy for therapy to exert its effect
Gestational diabetes • Screening and diagnosis In general, risk factor includes: 1. age>25y 2. BMI > 25 3. previous GDM 4. Family hx of DM in 1st degree relative 5. previous macrosomic baby (<4 kg) 6. polyhydramnio 7. large for date baby in current pregnancy 8. previous unexplained stillbirth
Gestational diabetes Screening Fasting / random glucose/ glucose challenge test(50gm) Diagnosis Glucose challenge test (75gm/100gm ?)
Gestational diabetes • Diagnosis WHO criteria 1998, 75 gm glucose fasting 2 hr (mmol/L) Impaired fasting glucose 6.1-6.9 IGT <or =7 and 7.8-11 DM >or = 7 or > or=11.1
Gestational diabetes • Incidence 2-9% more common in Asian and Indian women In developed countries, increasing trend because of epidemic of obesity
Gestational diabetes Clinical significance of GDM • High incidence of macrosomia, and adverse pregnancy outcomes, • A significant proportion(30%) identified as GDM in fact have DM before pregnancy
Gestational diabetes • Women with glucose intolerance just above normal range are at low risk for pregnancy complications, those with more severe glucose intolerance approaching the criteria of diabetes are at risk of neonatal complications
Fetal complications • Macrosomia (>4 kg) risk is 16-29% as compared to 10% in control • Increase in caesarean delivery, intrumental deliveries ( forceps/vacuum), birth trauma, such as brachial plexus injuries , clavicular fractures • Increase in neonatal hypoglycemia (24% ), hyperbilirubinemia, hypocalcemia, polycythemia • Children are at risk of type 2 DM and obesity in life
Maternal complications • Increase risk of hypertensive disorders • Increase risk of caesarean and intrumental deliveries • Increased Risk (40-60%) of developing type 2 DM within10-15 yr.
Gestational diabetes Does treatment improves outcomes? Conflicting results 1. Cochrane datebase systemic review 2005 (3 studies only) no difference in outcomes except neonatal hypoglycemia 2. Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS study) 2005 ( 490/510 subjects) treatment of diabetes reduces serious perinatal morbility and may improve the woman’s health-related quality of life
Gestational diabetes • Large randomized study on going HAPO trial in USA (Hyperglycemia and Adverse Pregnancy Outcome study)
Gestational diabetes Management • Management similar as preexisting DM • Need for glucose monitoring • Start with Diet control • Commence insulin for poor control • Delivery plan individualised
Gestational diabetes • In view of risk of developing type 2 DM the woman should be screened annually for DM on yearly basis.
Diabetes and PregnancyConclusion • Preexisting DM in pregnancy • Good glucose control is important for decreasing morbidities • Insulin is still the gold standard of tx in pregnancy • Increasing evidence for clincial effectiveness for treatment with oral hypoglycemic agents
Diabetes and pregnancyconclusion (2) Gestational diabetes • no consensus • The morbidities increases as glucose level approaching the diagnosis as DM • Possible that treatment improves outcomes • Overlap with preexisting DM, esp type2 • Long term implication for health of the mother and baby