Pregnancy with beta thalassemia

Dr. Mamuni Sultana Rony
Bangladesh

1. Pregnancy with beta thalassemia Dr. Mamuni Sultana Registrar Department of Obs. & Gynae Khulna Medical College Hospital

2. Particulars of the patient Name : Mrs. Lipica Age : 25 years Religion : Shanaton Occupation: Housewife Socioeconomic condition: Middle class Address : Pabla , Doulotpur , Khulna Husband Name : Mahafuz Mollah Date of admission : 10/06/15 Date of examination : 10/06/15

3. Chief complaints 1. Amenorrhoea for 38 weeks. 2.Less fetal movement for 1 day 3. Known case of beta thalassemia major for 9 years.

4. History of present illness According to the statement of the pt. she was amenorric for 38 wks. Her pregnancy was confirmed by urine test. She was in regular antenatal check up and was duly immunized . Her pregnancy was uneventful up to 16 wks. Then she developed generalised weakness and anorexia. For this reason she took 3 units of blood transfusion after getting admission in Obstertric department

5. During her subsequent antenatal check up she received total 10 units of blood after getting admission total 3 times in KMCH. She was non diabetic & normotensive .

6. History of past illness She had ill health , generalized weakness and pallor since her childhood and took 3 units of blood at her 15 years of age and diagnosed as a case of beta thalassemia major in 2006. Science then she took blood transfusion several time including during and after her previous pregnancies.

7. Family History No history of consanguinous of marriage. Neither her family members nor her husband was investigated for thalassemia or other hemoglobinopathies .

8. Obs. History Married for: 12 Years Para: 2(VD)+0 Gravida : 3 rd Age of last child: 5 years None of them was investigated for thalassemia or other hemoglobinopathies . Menstrual history MP/MC: Regular MF: average L.M.P: 17/09/14 E.D.D: 24/06/15

9. General examination Appearance- Anxious, ill looking Body built- Below average Anaemia - Mild Jaundice- Absent Cyanosis- Absent Oedema - Absent Dehydration- Absent Temperature- Normal( 98 F) Pulse-68/min B.P-120/70 mmHg Height- 4 feet 8 inch

10. Thyroid gland- not enlarged Lymph node- not palpable Breasts- shows normal pregnancy changes. Cardiovascular system- reveals no abnormality Other systems- Seems to be normal.

11. Per abdominal examination FH- 36 wks F.M- present Presentation- Cephalic Lie- Longitudinal Liquor- Seems to be less than adequate F.H.R- 140 beats/min

12. Per vaginal examination Cervix- Soft, posterior Os- Parous Station- High up Membrane- Intact Pelvis – Seems to be adequate

13. Clinical diagnosis 3 rd Gravida 38 weeks pregnancy with thalassemia major with IUGR with oligohydramnios

14. Investigations Ix Date Value Hb% 03.02.15 4.9 gm/dl 11.03.15 7 gm/dl 13.04.15 6.9 gm/dl PBF 03.02.15 Hemolytic anemia S. ferritin level 09.02.15 260 ngm /ml USG of pregnancy profile 08.02.15 11.03.15 Hepatospleeenomegaly IUGR with Oligohydramnios

15. Obstetric management LUCS with BLTL done on 11.06.15 due to 3 rd Gravida 38 weeks pregnancy with thalassemia major with IUGR with oligohydramnios . Baby note: Sex: Male Weight: 2 kg Liquor: Less A pgar score: 1 8 5 10 No visible congenital anomaly

16. Beta Thalassaemia Epidemiology More than 70000 babies are born with thalassaemia worldwide each year. 100 million individuals asymptomatic thalassaemia carriers.

17. Previously, the community affected was principally from Cyprus Mediterranean.

18. currently the Asian communities of India Pakistan Bangladesh account for 79% of thalassaemia births with only 7% occurring in the Cypriot population

19. The basic defect Reduced globin chain synthesis with the resultant red cells having inadequate haemoglobin content.

20. Pathophysiology Extravascular haemolysis due to the release into the peripheral circulation of damaged red blood cells and erythroid precursors because of a high degree of ineffective erythropoiesis . β thalassaemia major homozygous thalassaemia results from the inheritance of a defective β globin gene from each parent a severe transfusion-dependent anaemia . β thalassaemia trait ( thalassaemia minor) heterozygous state, mild to moderate microcytic anaemia no significant detrimental effect on overall health. Thalassaemia intermedia group of patients with β thalassaemia whose disease severity varies.

21. Modern treatment Splenectomy is no longer the mainstay of treatment The cornerstones of modern treatment in β thalassaemia are Iron chelation therapy

22. stem cell transplantation The only treatment protocol that can cure thalassemia is stem cell transplant. Transplant of blood and marrow stem cell can replace abnormal stem cells with healthy donor cells.

23. Experimental In- Utero Gene Therapy Researchers are striving to find new treatments For instance gene therapy- to insert a healthy hemoglobin gene into stem cells in bone marrow. This would allow people to create their own normal red blood cells and Hb

24. Multi organ damage Multiple transfusions cause iron overload resulting in dysfunction Hepatic

25. Cardiac Cardiac failure primary cause of death in over 50% of cases

26. Endocrine anterior pituitary Puberty is often delayed and incomplete Low bone mass Subfertile due to hypogonadotrophic hypogonadism require ovulation induction therapy with gonadotrophins to achieve a pregnancy

27. Risks to the mother and baby Mother Cardiomyopathy Diabetes mellitus Hypothyroidism Hypoparathyroidism

28. Fetal Fetal growth restriction (FGR) Intrauterine death

29. Beta Thalassaemia in Pregnancy Preconceptual care Genetic screening Screening for end-organ damage Optimisation of complications

30. Genetic screening If the partner is a carrier of a haemoglobinopathy that may adversely interact with the woman’s genotype then genetic counselling should be offered.

31. In vitro fertilisation / intracytoplasmic sperm injection (IVF/ICSI) with a pre-implantation genetic diagnosis (PGD) should be considered in the presence of haemoglobinopathies in both partners

32. pre-implantation genetic diagnosis (PGD) chorionic villus sampling amniocentesis

33. Iron chelation therapy prolonged period of iron chelation therapy may be required to control iron overload prior to both induction of ovulation Pregnancy Aggressive chelation in the preconception stage reduce and optimise body iron burden reduce end-organ damage

34. Pancreas Diabetes is common in women with thalassaemia . Good glycaemic control is essential prepregnancy . Women with established diabetes mellitus should ideally have serum fructosamine concentrations < 300 nmol /l for at least 3 months prior to conception. This is equivalent to an HbA1c of 43 mmol/mol.

35. Thyroid Thyroid function should be determined. The woman should be euthyroid prepregnancy Hypothyroidism is frequently found Untreated hypothyroidism can result in maternal morbidity perinatal morbidity and mortality.

36. Heart All women should be assessed by a cardiologist with expertise in thalassaemia and/or iron overload prior to embarking on a pregnancy.

37. Performed Echocardiogram ECG T2* cardiac MRI.

38. Liver Women should be assessed for liver iron concentration using a FerriScan ® Liver T2*. Ideally the liver iron should be < 7 mg/g (dry weight) ( dw ).

39. Liver and gall bladder (and spleen if present) ultrasound to detect cholelithiasis liver cirrhosis due to iron overload or transfusion-related viral hepatitis.

40. Bone density scan All women should be offered a bone density scan to document pre-existing osteoporosis. Serum vitamin D concentrations should be optimised with supplements if necessary.

41. Red cell antibodies ABO and full blood group genotype and antibody titres should be measured

42. Medications should be reviewed preconceptually Iron chelators deferasirox and deferiprone ideally discontinued 3 months before conception.

43. All bisphosphonates contraindicated in pregnancy and should ideally be discontinued 3 months prior to conception

44. Immunisation and antibiotic prophylaxis Hepatitis B vaccination is recommended in HBsAg negative women who are transfused or may be transfused Hepatitis C status should be determined.

45. All women who have undergone a splenectomy should take penicillin prophylaxis or equivalent.

46. All women who have undergone a splenectomy should be vaccinated for pneumococcus Haemophilus influenzae type b if this has not been done before

47. Supplements recommended Folic acid (5 mg) is recommended preconceptually to all women to prevent neural tube defects.

48. Antenatal care Specialist input delivered for women with thalassaemia monthly until 28 weeks of gestation fortnightly thereafter Both thalassaemia and diabetes monthly assessment of serum fructosamine Specialist cardiac assessment at 28 weeks of gestation thereafter as appropriate. Thyroid function should be monitored

49. Recommended schedule of ultrasound scanning Viability scan at 7–9 weeks of gestation. Routine first-trimester scan (11–14 weeks of gestation) Detailed anomaly scan at 20 weeks of gestation.

50. Serial fetal biometry scans (growth scans) every 4 weeks from 24 weeks of gestation. BPD AC FL BPD AC FL

51. Transfusion regimen All women with thalassaemia major should be receiving blood transfusions on a regular basis aiming for a pretransfusion haemoglobin of 100 g/l. Transfuse every 2–5 weeks, maintaining pre-transfusion Hb above 9–10.5 g/dl, but higher levels (11–12 g/dl) may be necessary for patients with heart complications. Keep post-transfusion Hb not higher than 14–15 g/dl.

52. Antenatal thromboprophylaxis recommended Thalassaemia with splenectomy or platelet count greater than 600 x 109/l Low-dose aspirin (75 mg/day). Thalassaemia with splenectomy and platelet count greater than 600 x 109/l Low-molecular-weight heparin as well as Low-dose aspirin (75 mg/day).

53. Optimum antenatal management of iron chelation therapy Teratogenic Deferasirox Deferiprone Desferrioxamine Short half-life Safe for infusion during ovulation induction therapy. Should be avoided in the first trimester owing to lack of safety data Used safely after 20 weeks of gestation at low dose

54. Myocardial iron Highest risk of cardiac decompensation Low-dose subcutaneous desferrioxamine (20 mg/kg/day) on a minimum of 4–5 days a week from 20–24 weeks of gestation Liver iron Low dose desferrioxamine iron chelation from 20 weeks. (liver iron > 15 mg/g dw as measured by MRI)

55. Intrapartum care Intravenous desferrioxamine 2 g over 24 hours should be administered for the duration of labour . Continuous intrapartum electronic fetal monitoring Thalassaemia in itself is not an indication for caesarean section. Active management of the third stage of labour is recommended to minimise blood loss

56. Postpartum care High risk for venous thromboembolism . low-molecular-weight heparin should be administered for 7 days post discharge following vaginal delivery 6 weeks following caesarean section Breastfeeding is safe and should be encouraged.