Medical Disorders of Pregnancy

1. Medical Disorders of Pregnancy Hassan A Shehata MRCOG MRCPI Consultant Obstetrician, Gynaecologist & Obstetric Physician Epsom & St. Helier University Hospitals NHS Trust St. Helier’s Hospital – 3 October 2006

2. CEMACH 2002-2004 Breakdown of direct causes

3. CEMACH 2002-2204 Breakdown of indirect causes

4. CEMACH 2002-2004 Leading Causes of Death

5. Diabetes - Classification

6. Effect of pregnancy on DM • Normal pregnancy • Fall in fasting BG • Rise in post-prandial BG • Insulin resistance & relative glucose intolerance • Glucose tolerance decrease with increasing gestation due to hPL, glucagon & cortisol • Renal threshold for glucose falls • Rise in insulin requirements x 2 • Deterioration in nephropathy (reversible) • Two fold risk of progression of retinopathy

7. CEMACH 2006 • Women in UK with pre-existing (type 1 or type 2) diabetes are poorly prepared for pregnancy • The recent CEMACH report highlighted the fact that across the country, only 1 in 3 women were documented as receiving any kind of preconception counselling or having a preconception HbA1c measurement • The level of uptake of folic acid supplements before conception was very poor (39%) which is particularly concerning given the increased risk (3.4-fold) of neural tube defect • Even amongst those take folic acid, few were prescribed the higher dose (5mg) as recommended by the National Service framework (NSF) Diabetes

8. Type 2 DM • Previous reports of type 2 diabetes being perceived as far less common in women of childbearing age as well as less serious condition • However, it has become increasingly apparent that both these perceptions are mistaken • The prevalence of type 2 diabetes in young people is increasing and accounts for over a 1/4 of pregnant women with pre-existing diabetes and in some parts of the country including London this rises to 45% • Over-representation of black, Asian and other minority groups (49% compared with only 9% of women with type 1 diabetes) and a strong association with social deprivation • It is now clear that adverse pregnancy outcomes are as common in women with type 2 diabetes as those with type 1 diabetes • Risk of perinatal mortality and congenital malformation are equivalent and babies of women with type 2 diabetes are more likely to be large in size for gestational age and delivered pre-term

9. Feto-maternal blood glucose relationships • Glucose crosses the placenta by a process of facilitated diffusion • Fetal plasma glucose levels are similar to those of the mother • Fetal insulin secretion occurs from 10 weeks gestation • There is a brisk fetal insulin response to raised plasma glucose levels in diabetic pregnancy • Sustained fetal hyperglycaemia secondary to maternal hyperglycaemia can result in fetal -cell hyperplasia

10. HbA1c • Level is raised in diabetes • Reflects diabetic control over the previous 2 or 3 months • Estimation has proved a valuable additional aid to be on the look-out for major congenital abnormalities

11. Effect of pre-existing DM on pregnancy • Increased risk of congenital abnormalities • Increased perinatal mortality • late “unexplained” intrauterine death • Increased risk of pre-eclampsia • Increased perinatal morbidity • Prematurity • Macrosomia

12. Congenital Abnormalities • 2 - 4 fold increase ie. 10% risk • Directly related to glycaemic control • Correlated with HbAIC • Very small risk if HbAIC < 50% above upper limit of normal • Sacral agenesis • CHD • Skeletal / NTD

13. Perinatal Mortality • IUD is rare • Related to fetal acidaemia • Related to maternal BG • Cannot predict with • biophysical profile • CTG • Umbilical artery Doppler

14. Perinatal Morbidity

15. Management of DM in Pregnancy • Pre-pregnancy counselling • Combined clinic (single physician + obstetrician) • HBGM with meter • Aim for normoglycaemia • fasting 4-6 mmol/l • 1 hr pp 4-8 mmol/l • 2 hrs pp 4-7 mmol/l • Diet +/- Insulin • Monitor control of IDDM with HbA1C • Glucagon kit for IDDMs • Screen for retinopathy

16. Pre-pregnancy counselling (PCC) • Optimize glycaemic control • Risk of major congenital malformations is increased x 3/4. • Risk correlates with HbA1C. • Assess presence / severity of complications • Hypertension • Retinopathy • Nephropathy • Stop oral hypoglycaemics

17. PCC……Contraindications to pregnancy in DM • Ischaemic Heart Disease • Untreated proliferative diabetic retinopathy • Hypertension and severe renal impairment (Cr > 250) • Severe gastroparesis

18. Obstetric Management • Ultrasound • to detect congenital abnormalities • to assess fetal growth / polyhydramnios • Screen for pre-eclampsia • Timing of delivery • Risk of IUD vs. risk of RDS • Risk of macrosomia and shoulder dystocia vs. CS • 38 - 40 weeks • Caution with steroids and beta-sympathomimetics

19. Intrapartum and postpartum care • Continuous FHR monitoring • IV dextrose and variable IV insulin • BG 5-8 mmol/l • Halve rate of insulin post partum • Pre-pregnancy insulin SC dose when eating • Prophylactic antibiotics if CS • Neonatal BG 4 hours • Feed neonate early

20. Recommendations • Plan pregnancy • Pre-pregnancy counselling • Tertiary centre / joint clinic / diabetes nurse specialist / diabetes midwife/ dietician • Monitor using post-prandial BGs • Basal bolus insulin regimen • Monitor fetus and time delivery • Post-pregnancy counselling

21. Hyperthyroidism • Prevalence in pregnancy is up to 0.2% • Grave’s disease - up to 90% of cases • Untreated - dangerous for mother & baby

22. Hyperthyroidism - Clinical Features • Many of the typical features are common in normal pregnancy • Discriminatory features include weight loss, tremor, a persistent tachycardia, lid lag and exophthalmos • If thyrotoxicosis occurs for the first time in pregnancy, it usually presents late in the first or early in the second trimester.

23. Normal ranges for TFT in pregnancy

24. Hyperthyroidism - Effect of Pregnancy • Thyrotoxicosis often improves during pregnancy especially in the second and third trimesters. • Exacerbations may occur in the first trimester, possibly related to hCG production, and in the puerperium

25. Hyperthyroidism - Effect on Pregnancy • If severe and untreated, it is associated with inhibition of ovulation and infertility • Higher incidence of miscarriage, placenta abruption, pre-term delivery and PET • Neonatal hyperthyroidism, prematurity, intrauterine growth retardation, fetal death and stillbirths • Poorly controlled thyrotoxicosis may lead to a thyroid crisis (‘storm’) in the mother and heart failure, particularly at the time of delivery. • The possibility of retrosternal extension of a goitre which can cause tracheal obstruction

26. Hyperthyroidism - Diagnosis • A raised free T4 or free T3. Normal pregnant ranges for each trimester must be used • TSH is suppressed, although this may be a feature of early pregnancy. • Differentiation from hyperemesis gravidarum may be difficult

27. Hyperthyoidism - Management • Grave’s disease often improves, flares postpartum • CBZ (up to 15mg) & PTU (up to 150mg) cross placenta • -Blockers are safe • Thyroidectomy is rarley necessary:- • Who fail to achieve euthyroidism • intolerant to drugs • with dysphagia or stridor related to a large goitre • with confirmed or suspected thyroid malignancy

28. Hypothyroidism • Prevalence is in the order of 1% • Commonest is autoimmune destructive thyroiditis • Untreated - associated with infertility, miscarriage and fetal loss

29. Hypothyroidism - Clinical Features • Features are common in normal pregnancy • Discriminatory features in pregnancy are cold intolerance, slow pulse rate and delayed relaxation of the tendon (particularly the ankle) reflexes. • It is associated with other autoimmune diseases, for example, pernicious anaemia, vitiligo and type-I diabetes mellitus

30. Hypothypidism - Diagnosis • Low free T4. • The TSH is raised, although this may be a feature of normal late pregnancy, or occasionally early pregnancy • The finding of thyroid autoantibodies may help confirm the diagnosis, but these are present in 10-20% of the population and should not be used in isolation

31. Hypothypidism - Effect of Pregnancy • Pregnancy itself probably has no effect on hypothyroidism • If the dose does need to be increased in pregnancy, this is usually because of inadequate replacement prior to pregnancy

32. Hypothypidism - Effect on Pregnancy • Severe and untreated - inhibition of ovulation and infertility. • Those who do become pregnant and remain untreated have an  rate of miscarriage, fetal loss, PET & LBW • An association between untreated hypothyroidism in the mother and reduced IQin the offspring. • With adequate replacement, the maternal and fetal outcome is usually good

33. Hypothyroidism - Management • Small amounts of thyroxine cross the placenta - fetus is not at risk • Most will be on maintenance doses of thyroxine of 100-150 ug/day • Euthyroid women will not usually require any adjustment to dose • TFT should be checked in all women, ideally pre-conceptually, or at least during the first trimester • Replacement with thyroxine should begin immediately • With adequate replacement, thyroid function should be checked once in each trimester

34. Epilepsy – Effect of Pregnancy • About 1/3 of women experience an increased frequency of fits • Poorly controlled epileptics are more likely to detriorate • In most (54%), the frequency of fits is not altered

35. Epilepsy – Effect on Pregnancy • There is no increased risk of miscarriages • The fetus is relatively resistant to short episodes of hypoxia • The risk of the child developing epilepsy is increased (4%) • Teratogenic effects of anticonvulsants

36. Epilepsy - Anticonvulsants • All cross the placenta and are teratogenic • Not much difference in the risk of the four principle AEDs • Background risk = 3% • Untreated epileptic = 4% • 1 drug = 7% • 2 or more drugs = 15% • Val + carb + phenytoin = 50%

37. Epilepsy - Management • Assess need for treatment • Optimize control – treat patient not drug level • Monotherapy if possible • Counsel re teratogenesis • Give folate 5 mg / day

38. Migraine • It can occur as a pregnancy-related phenomenon without any prior history • Pre-existing migraine (50-80%) often improves in pregnancy • Hemiplegic migraine may mimic TIA • Ergotamine, sumatriptan & pizotifen should be avoided • Low-dose aspirin, beta-blockers, tricyclic antidepressants & calcium antagonists may be used for prophylaxis

39. Asthma – Effect of Pregnancy • May improve, deteriorate or remain unchanged • Mild disease – unlikely problems • Possible postnatal deterioration • Deterioration of disease is commonly caused by reduction or cessation of medication

40. Asthma – Effect on Pregnancy • Mostly no adverse effects • Severe, poorly controlled asthma may adversely affect the fetus • No association with PET, prem. labour, LBW, IUGR and neonatal morbidity

41. Asthma - Management • Treatment differs little from Mx in non-pregnant patient • Education and reassurance concerning the safety of asthma medications • Inhaled, oral and intravenous steroids and inhaled, nebulized and intravenous beta-agonists are safe • Do not withold a chest X-ray if necessary

42. Physiological changes of thrombotic/fibrinolytic system • Increase in levels of factors VIII, IX, X and fibrinogen • Decrease in fibrinolytic activity • Decrease in antithrombin III and protein S • Venodilation and decreased flow in lower limbs leads to venous stasis

43. Pulmonary Embolism (PE) • PE is the major cause of maternal death • 3% of direct deaths • 1.4 deaths per 100,000 maternities • 35 women died from TED in 1997-9 • 31 PE & 4 cerebral thrombosis • 13 antenatally (8 in 1st trimester) • 17 postnatally (7 after Caesarean, 10 after vaginal delivery

44. Acute Episodes -  PE • Chest X-ray • Arterial blood gas analysis pO2 - 13 kPa (100mmHg) standing, 11kPa (83mmHg) supine pCO2 - 4 kPa (30mmHg) • SO2 drop by > 6mmHg • Electrocardiography • V/Q scan or spiral CT • D dimers not helpful • Thrombophilia screen

45. Estimated radiation to the fetus and excess risk of childhood cancer following common diagnostic procedures Estimated radiation to the fetus (mGy) Probability of fatal cancer to age 15y Conventional X-ray Chest 0.01 <1 in 1000,000 Pelvis 1.1 1 in 300,000 Skull 0.01 <1 in 1000,000 Spine 1.7 1 in 20,000 Computerized Tomography Chest (inc. spiral) 0.06 1 in 560,000 Pelvimetry 0.2 1 in 170,000 Nuclear Medicine Lung perfusion (Tc 99m) 0.2 1 in 170,000 Lung ventilation (Tc 99m) 0.3 1 in 110,000 Childhood fatal malignancy background risk is 1:650,000

46. V/Q scan Spiral CT

47. Pathological MRI specimen

48. TED - Mx • If DVT or PE is diagnosed [or strongly suspected], anticoagulation with heparin should be commenced • Therapeutic-dose i.v. heparin or LMWH for ~ 12 weeks • Then prophylactic LMWH for up to 6 weeks postpartum or longer (total of 6 months)

49. Drug transfer • Most drugs have a molecular weight below 1000 daltons (D) • Drugs  1000 D cross the placenta ( 600 D cross easily) • Main determinant of the drug concentration in the embryo/fetus is the mother's blood concentration • Other factors:- • lipid solubility & protein binding • degree of ionization at physiologic pH • placental blood flow & surface area available for transfer

50. The processes that govern the passage of a drug into milk are similar to the placenta • maternal serum concentration is the main determinant • the milk pH is slightly acidic in comparison to serum pH; so weak bases could become trapped in milk (ion trapping)