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Update in Diabetes and Pregnancy: Bridging the Care Between Providers. Dr. Erin Keely Chief, Division of Endocrinology and Metabolism The Ottawa Hospital Professor, Depts of Medicine and Obstetrics/Gynecology University of Ottawa. Objectives:.
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Update in Diabetes and Pregnancy:Bridging the Care Between Providers Dr. Erin Keely Chief, Division of Endocrinology and Metabolism The Ottawa Hospital Professor, Depts of Medicine and Obstetrics/Gynecology University of Ottawa
Objectives:. At the end of this presentation I hope you will be able to: Appreciate the importance of preconception care for women with diabetes and obesity Recognize the similarities and differences between type 1 and type 2 diabetes in pregnancy Identify new GDM diagnostic guidelines may be coming Appreciate the importance of the “fourth trimester” for women with gestational diabetes
Classification of Diabetes Pre-gestational Type 1 Type 2 Gestational other
What’s the difference between type 1 and 2 for pregnancy? Comorbidities type 1 - autoimmunity, thyroid disorders, nephropathy type 2 - hypertension, hyperlipidemia, obesity, PCOD Treatment oral agents vs. insulin type 2 often on statins, multiple antiHTN Pre-pregnancy care type 2 may be considered less severe older, often recent immigrants may have low expectations of fertility
Confidential Enquiry into Maternal and Child Health (2002-2004)
Preconception care in managed care setting • Women 18-45 yrs enrolled in TRIAD study • Asked to recall if had discussions about glycemic control before conception and use of family planning • 52% of women recalled discussions about preconception glucose control, 37% recalled family planning advice • Patient age (OR 0.91, CI 0.86-0.96) and BMI (OR 0.96, CI 0.93-0.99) predicted glucose control counselling Younger age and lower BMI more likely to receive counselling Kim, Am J Obstet Gynecol, 2005
Women’s perceptions on becoming pregnant • n=15, type 1 • Intention of becoming pregnant is a continuum • Not planned/unplanned; wanted/unwanted; • Use term ?readiness • Some women felt anxious after formal prepregnancy planning sessions • Conclusions • Advice must be tailored to each women’s current situation • Build on the patients resources • Health professionals normally seeing women in relation to their diabetes may be the best Griffiths, British J of General Practice, 2008
Personal experiences of those who don’t come for prepregnancy care • n=29 (21 type 1, 8 type 2) • Semi-structured interviews • Reasons for not attending pre-pregnancy care • Got pregnant quicker than expected (45%) • Fertility concerns (31%) • Negative relationships with providers (21%) • Fear of disappointment, wanting pregnancy to be normal (17%) • Logistics/finances (10%) Murphy, Diab Medicine 2010;27:92-100
Interpregnancy care • Personal experience of a poor pregnancy outcome does not encourage and may even discourage high-risk women from attending preconception care • Need to provide postpartum support and ongoing care • what would help you be bettered prepared for your next pregnancy? • what would make this difficult?
Obstetrical risks andobesity Infertility Failure of contraception Gestational or type 2 diabetes Preeclampsia Risk of c-section Surgical complications Wound Respiratory Thrombosis anaesthesia First trimester loss Late pregnancy loss Macrosomia Congenital anomalies Neural tube Cardiac More difficult to diagnose Decreased breast feeding Longterm maternal and childhood obesity
Treatment of type 2 diabetes may result in conception -metformin and glitazones are potent fertility treatments
Diabetes and Congenital Anomalies • Hyperglycemia • Obesity • Medications
Glucose is a teratogen Sacral agenesis
+ve pregnancy test MD appt The first prenatal visit is months too late!
HgbA1c and Congenital Anomalies Target: A1c < 0.07
Poor pregnancy outcome in women with type 2 diabetes Clausen et al, Diab Care 2005;28:323-328 Maybe it isn’t just the glucose • 61 women with type 2 vs. 240 with type 1 from 1996-2001 type 2 type 1 • Perinatal mortality 6.7% vs 1.7% • Cong anomalies 6.7% vs 1.7% • HgbA1c 6.8% vs 7.0%
Increased risk of congenital anomalies and obesity • Many studies support increased risk • Population based case-control, Metropolitan Atlanta Congenital Defects program • Overweight (BMI 25.0-29.9) • Cardiac 2.0 (1.2-3.1) • Multiple anomalies 1.9 (1.1-3.4) • Obese (BMI ≥ 30) • Spina bifida OR 3.5 (1.2-10.3) • Omphalocele 3.3 (1.0-10.3) • Cardiac 2.0 (1.2-3.4) • Multiple anomalies 2.0 (1.0-3.8) Watkins et al., Pediatrics 2003
For every 1 increase in BMI (kg/m2), the risk of a neural tube defect increases 7% Watkins, Pediatrics 2003 The epidemic of obesity may be leading to an epidemic of birth defects 20
Will more folate help? Folate levels have decreased 16% since fortification of cereal (NHANES data) MMWR weekly Jan 5, 2007 NTD increased 1.2 fold per 10 kg maternal weight even after fortification Ray, Am J Obstet Gynecol 2005 Obese women less likely to eat cereals, vegetables Laraia, Public Health Nutr 2007 Obese women have lower serum folate levels with same intake – need to take an additional 350 ug/day Mojtabai, Eur J Epidemiol 2004
Recommendation Benefit of >0.4 mg folate supplementation has not been studied ACOG Committee Opinion, Obstet Gynecol 2005 5 mg folate replacement preconception for all women with BMI>35, women with diabetes Wilson, JOGC 2007; CDA Clinical Practice Guidelines, 2008
ACE inhibitor exposure in pregnancy Bowen, Am J Obstet Gynecol 2008
Risk of Congenital anomalies and ACEI Any (n=18) 2.71 RR (1.72-4.27) CV (n=7) 3.72 RR (1.89-7.30) CNS (n=3) 4.39 RR (1.37-14.02) Cooper, NEJM 2006
Treatment of dyslipidemia • Statins • Limited and conflicting data • No evidence of harm, but no evidence of benefit • Fibrates (PPAR agonists) • Clearly cross placenta • Only in severe hypertriglyceridemia
Oral hypoglycemics for type 2 diabetes in pregnancy Glyburide don’t cross placenta Likely safe, but ineffective in T2DM Metformin crosses placenta Possible benefit in first trimester Glitazones Cross placenta especially after 10 weeks Limited safety data
Change to insulin prepregnancy unless using metformin for ovulation induction
Diabetes complications Microvascular retinopathy nephropathy neuropathy macrovascular coronary artery disease cerebrovascular disease peripheral vascular disease
Retinopathy most studies suggest worsening laser before pregnancy - stable for 6 months
Nephropathy Normally increase GFR 50% in pregnancy may not be able to increase GFR, GFR may decline Will increase Uprotein excretion If serum creatinine >125 umol/L risk of permanent/prolonged worsening High risk of superimposed pre-eclampsia
Infections Increased antepartum urinary, respiratory asymptomatic bacturia should be treated increased postpartum c-section incision mastitis
Effects on glycemic control Marked increase in insulin resistance Due to placental effect - GOOD thing increase in cortisol, prolactin, hPL insulin dosages increase 2-3 fold Increased risk of unrecognized hypoglycemia Especially first trimester Risk of seizures, LOC Increased risk of diabetic ketoacidosis (T1) high fetal mortality Can be precipitated by steroids for lung maturity
1st Trimester issues Glycemic control HBGM qid premeal 4-6 mmol/L, 2 hr pc < 8 hypoglycemia symptoms review diet/ hyperemesis reassess complications accurate dating of pregnancy (ultrasound)
2nd trimester issues Glycemic control insulin requirements start to increase complications watch BP, repeat urine, reinforce need for ophthamology FU fetal assessment level 2 and cardiac echo
3rd trimester issues Glycemic control complications worsening hypertension/superimposed pre-eclampsia fetal assessments
As the placenta matures a decrease in insulin requirements starts to occur around 38 weeks gestation Decrease in the mother’s insulin requirements after delivery of the placenta makes the first postpartum day a high risk period for hypoglycemia Labour and delivery and postpartum
Neonatal hypoglycemia is positively correlated with maternal plasma glucose at delivery Study found no cases of neonatal hypoglycemia if the maternal plasma glucose at delivery was <7.1 mmol/L. Acta paediatri Scand 74:268-273, 1985 Study found no relation between neonatal glucose and maternal glucose until maternal glucose > 9 mmol/L. ACOG 99;4:537-541, 2002 Neonatal hypoglycemia dependent on maternal glucose at delivery
Consistency in peripartum insulin orders may be difficult due to multiple caregivers at different levels of training If not done consistently may be completed by someone not familiar with patient’s glucose control, insulin management and preference for self-care Appropriate regimens may not be instituted for safe postpartum management Peripartum insulin orders
Peripartum Discontinue s.c. insulin when in active labour or if having elective c-section use IV insulin peripartum restart s.c. insulin when eating 2/3 of prepregnancy dose
Gestational Diabetes Carbohydrate intolerance with onset or first recognition in pregnancy 2-4% of pregnancies Same risk factors as type 2 diabetes
Multinational U.S. centred observational study Designed to clarify the risk 75 gram OGTT 24-32 weeks GA Excluded if FBS > 5.8 or 2 hr > 11.1 Remainder of the women were observed No Rx, standard of care for delivery
HAPO > 23 000 women FBS 4.5 mmol/l 1hr GTT 7.4 mmol/l 2hr GTT 6.2 mmol/l 1° outcomes BW > 90%, 1° C/S, neonatal hypoglycemia, fetal hyperinsulinemia (cord c-peptide levels) 2 °outcomes Preterm birth < 37 wks, birth injury, NICU, ↑ bilirubin, preeclampsia What we would consider quite normal!
HAPO Perinatal risk increases in linear fashion even within a fairly normal range of glucose values association between glucose and adverse outcomes occurs even within limits not previously thought to be problematic or diagnostic for GDM
IADPSG Proposed New Diagnostic Criteria First prenatal visit measure FPG, A1C or random glucose on all or high-risk women diagnose overt diabetes in pregnancy if: Fasting ≥ 7.0 mmol/l A1c ≥ 6.5% Random plasma glucose ≥ 11.1 mmol/l (+confirmation) Diagnose GDM if FPG 5.1- 6.9 mmol/l If FPG < 5.1 mmol/l, retest at 24-28 wks Diabetes Care March 2010
IADPSG Proposed New Diagnostic Criteria At 24-28 weeks 75 g OGTT No 50 g screen only 1 abnormal value required cut-offs Fasting 5.1 mmol/L (5.3) 1hr 10.0 mmol/L (10.6) 2hr 8.5 mmol/L (8.9) Diabetes Care March 2010
Reasons to look for GDM index pregnancy macrosomia hypoglycemia in neonate fetal loss offspring type 2 dm obesity maternal - type 2 dm
Bottom Line for treatment Diet Home blood glucose monitoring Target fasting 3.8-5.2 mmol/l 1 hr pc 5.5-7.7 mmol/l 2 hr pc 5.0-6.6 mmol/l Insulin first Oral agents second Glyburide More effective Concern of long term consequences has limited use Metformin Likely safe despite crossing placenta Less effective