1. Diabetes in pregnancy Sham Acharya Clinical Director GNC Diabetes Staff Endocrinologist JHH

2. Objectives Diabetes (type 1 and type 2) and pregnancy What you need to know from preconception to post natal journey Maternal risks Foetal risks Treatment targets and how we prefer to do it Gestational Diabetes Maternal and foetal issues How to diagnose and manage?

3. Case History Mel is a 29yrs old PhD student in Chemistry. She has had type 1 Diabetes for 18 years. HbA1c has been around 8.5%. She is busy and has not seen any specialist for some time. She is an infrequent visitor. She is recently married and she comes to see you to ask about pregnancy in Diabetes.

4. Her questions…. Can I become pregnant with Diabetes? Is there an increased risk of miscarriage? What are the risks for my baby? If I have a hypo would my baby suffer? What medications are safe? What happens to me and my diabetes during pregnancy? I am not on any contraception – can I conceive now?

5. Maternal complications (Type 1 and Type 2 DM) Pregnancy effects on Diabetes  Increased risk of DKA, hypoglycaemia, altered awareness  Increased risk of retinopathy, nephropathy, HT Diabetes effects on pregnancy  Miscarriage, PIH  Polyhydromnios  Pre-term labour, C-section  Use of steroids

6. Foetal complications Increased risk of congenital malformations -Neural tube defects, cardiovascular, renal anomalies Sacral agenesis Macrosomia Birth injuries -Shoulder dystocia, fractures, brachial plexus injuries, birth asphyxia Neonatal hypoglycaemia, seizures, jaundice Still birth

8. Teratogenic effect of hyperglycaemia in early pregnancy Depletion of myoinositol, increased free radicals Alteration of arachidonic acid metabolism Enhanced generation of NO an inducer of apoptotic cell death Most anomalies occur within 5-8 weeks of LMP Crucial to seek advice before pregnancy!

9. Congenital anomaly Overall 6-8% prevalence (3 times higher) If HbA1c is normal at conception, rate back to background risk Higher the HbA1c, higher the risk (40%) Poor glycaemia often result in miscarriage up to 50%

10. St Vincent Declaration 1989 “ Outcome of diabetic pregnancy should be equal to that of non diabetic pregnancy within 5 years” WHO, IDF, EASD and European governments joined together in this declaration

11. 13 Years after St Vincent Declaration…. CEMACH (Mary C M Macintosh BMJ 16 June 2006) 2359 pregnancy with DM in 231 hospital (2002-03) across England, Wales, NI 27% pregnancy were type 2 DM Peri natal mortality 31.8/1000LB (T1=T2) PNM 4times higher 141 major congenital anomaly (6%) Median HbA1cs - 7.9% - major congenital anomaly - 8% - still birth - 7.4% - normal healthy baby

12. CEMACH Factors associated with poor pregnancy outcome Maternal social deprivation Lack of contraceptive use in the 12 months before pregnancy No folic acid intake at any time in the 12 months before pregnancy Suboptimal approach of the woman to managing her diabetes Suboptimal preconception care Suboptimal glycaemic control at any stage before and during pregnancy Suboptimal maternity and diabetes care during pregnancy Suboptimal foetal surveillance of big babies

13. HbA1c in Early Diabetic Pregnancy and Pregnancy Outcomes A Danish population-based cohort of 573 pregnancies in women with type1 diabetes HbA1c (%) Percentage of Adverse Outcomes (95% CI) ≤7 1.2 (7.6-17) 7.1-817 (11-25) 7.9-8.919 (12-27) 9-10.235 (24-47) ≥>10.279 (60-91) Each 1% rise of HbA1c corresponds to 5.5% increased risk of an adverse outcome Nelsen G.I, Moller M, Sorensen H.T Diabetes Care 29:2612-2616 2006

14. Pre-conception advice and management

15. Initial visit Review medical history Type and duration of DM Previous DKA, Hypoglycaemia, hypo unawareness Retinopathy, neuropathy, nephropathy Hypertension Vascular problems (IHD) Other medical problems (thyroid) Menstrual history, previous pregnancy, contraceptive use Blood glucose patterns, frequency of testing Self management skills Support system including family and work environment

16. Pre-conception targets  HbA1c 6% or less but <7% mostly acceptable  Aim fasting glucose 4 -5.5mmol, post prandial <7mmol  Monthly HbA1c if planning pregnancy  Optimise insulin therapy -Basal-bolus or insulin pumps  Stop SU, Glitazone, Gliptin, Exenatide  Metformin is safe but discuss the limited evidence  Folic acid 5mg till 12 weeks of gestation  Discontinue ACEI, statins  Methyldopa if hypertensive

17. Once pregnancy confirmed See them urgently and regularly 2- 3 weekly review (preferably joint clinics with obstetricians, endocrinologist) First trimester – hypos are troublesome Insulin doses escalate second and third trimesters – almost double!

18. During pregnancy Aim fasting 4-5.5, post prandial 6-7mmol/l Aim HbA1c <6% Any glucose over 10mmol – check ketones – risk of DKA Low threshhold for admission if any concerns Retinal assessment, urine ACR each trimester Regular foetal monitoring, additional USD Aim to deliver around 39 weeks

19. Education

20. Structured educational program -IEP, EMPOWERMENT Dietitian (review calorie intake, carb counting) Educator review (hypos, sick day management, ketone testing, glucagon kit for family member) Handout DVD, info leaflet about pregnancy Review family and social support Smoking and alcohol

21. During delivery IV insulin, Dextrose and potassium Regular monitoring Obstetrics and neonatal specialist support Increased chance of operative delivery NICU Have post natal plan pre-delivery - if in doubt halve the insulin dose -breast feeding may need additional 25% insulin dose reduction If type 2 – may be able to discontinue insulin

22. Post-natal visit Recurrent hypos vs. poor control Increased risk of puerperal sepsis and DKA Contraception May be at risk of another unplanned pregnancy! Type 2 – may recommence OHA

23. Counselling Congenital anomalies; increased risk with poor control Increased risk of abortion (15%) Worsening acute and chronic complications of DM Increased risk of obstetric complications Risks to the foetus But…most would have a normal baby! Do not discourage pregnancy unless major contra- indications but always encourage a planned pregnancy

24. Gestational Diabetes By definition, the recognition of diabetes for the first time during pregnancy which disappears following delivery Different continents have different diagnostic methods and threshold because there is no single value of glucose that determines the absolute risks to baby or mother Opportunistic screening - Previous GDM -Previous macrosomia -Family history & ethnicity -Increasing maternal age and parity -Obesity Universal screening

25. Complications of Gestational Diabetes Foetal risks Macrosomia Birth injuries Still birth Neonatal hypoglycaemia Maternal risks Polyhydromnios, pre term labour Increased risk of operative delivery Increased future risk of type 2 diabetes

26. Diagnosis of GDM If previous history of IFG or IGT – Assume GDM and monitor and treat early High risk 12-16 weeks OGTT, repeat at 24-28 weeks if negative OGTT 24-28 weeks in all patients (if universal screening adapted) Diagnostic criteria Fasting: ≥ 5.5 1hr ≥ 10 2hr ≥ 8.0mmol/l Proposed changes with HAPO Fasting: ≥ 5.0 1hr ≥ 10 2hr ≥ 8.5mmol/l Newcastle 8% prevalence at present without universal screening Will increase the workload by additional 30% and if universal screening 130% increase in work load! We would expect around 500 pregnancies in a year!

27. Management Glycaemiac targets same as type 1 or type 2 Metformin may be an option Insulin 2 weekly review till delivery 6 weeks OGTT and follow up 50% risk of type 2 DM Breast feeding cuts the risk enormously!

28. Thank you