ANAEMIA IN PREGNANCY_NPMCN UPDATE COURSE JULY 2023-1.pptx

ANAEMIA IN PREGNANCY_NPMCN UPDATE COURSE JULY 2023-1.pptx

1. ANAEMIA AND HAEMOGLOBINOPATHIES IN PREGNANCY Abiodun S . ADENIRAN (FMCOG; FWACS; MD; MHPM) READER Obstetrics & Gynaecology Department, University of Ilorin/ University of Ilorin Teaching Hospital, Nigeria. UPDATE COURSE JULY 2023 by NPMCN

2. Outline Introduction Epidemiology Physiological changes in pregnancy and Anaemia Classification Approach to Management Current Research Questions Haemoglobinopathies Management of Haemoglobinopathies in Pregnancy Conclusion Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

3. Lecture Objectives Revise the epidemiology of anaemia in pregnancy Outline a rational approach to management of Anaemia in pregnancy Enumerate current Research Questions/ Issues on Anaemia in Pregnancy Discuss the management of pregnant women with Haemoglobinopathies Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

4. Introduction A naemia : fewer circulating red blood cells ( RBC) or a reduction in the concentration of haemoglobin with red uction in the O 2 -carrying capacity of the blood M ay follow redu ced production / increased RBC loss An important global maternal health problem and c ommonest medical disorder in pregnancy Important indirect cause of severe Maternal Outcome ( 61.2% of near-misses and 32.8% of maternal deaths ) in the Nigeria Near-Miss and Maternal Death Survey . 1 Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

5. Epidemiology Worldwide, an a emia affects approximately 1.62 billion individuals ≈ 24.8% of the total global population. 2 The highest prevalence of anaemia occur among pre-school children (47.4%) and pregnant women (41.8%) 2 Anaemia in pregnancy is considerably high ( ≈ 30–40%) even in high-income countries 2 compared to 35-75% in Africa, Asia and Latin America 90% Fe deficiency Anaemia , ≈ 5% Folate Deficiency Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

6. Epidemiology- 2 Important socio-demographic factors: Education, parity (low and high) , low social class, age (18-20years, > 35years), poor nutrition . Other important factors: 3 Infestation with intestinal parasite: ↑ 3.59 times No Iron and folic-acid supplementation: ↑ 1.82 times Women in third trimester of pregnancy: ↑ 2.37 times Women who had low dietary diversity score: ↑ 3.59 Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

7. Physiological changes in pregnancy vs. Anaemia Plasma volume: ↑50% Red Cell Mass: ↑ 1 5 -30 % Graph of Hb is ‘U-shaped ’ not linear Erythropoiesis : ↑MCV (up to 60fl) , MCHC↔ ↑ Fe utilization: ↓serum Fe & Ferritin, ↑ TIBC ↑Folate re q uirement Hb: ↓20g/L from pre-pregnany level Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

8. Etiologic classification 4 Blood loss Acute: APH Chronic: Hookworm, Bleeding Hemorrhoid or PUD Nutritional Iron, Folic acid or Vit B12 deficiency Bone marrow failure Aplastic anaemia Isolated secondary failure of erythropoiesis Drugs: Chloramphenicol, Zidovudine Haemolytic -Inherited Haemoglobinopathies Red cell membrane defects Enzyme deficiency:G6PD -Acquired Infections: Malaria, HIV Immune haemolytic anaemia Non-immune haemolytic anaemia Systemic diseases: renal, liver Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

9. Morphological classification 4 Hypochromic Microcytic Fe deficiency Thalassemia Sideroblastic anaemia Anaemia of chronic disorders Lead poisoning Macrocytic Folic acid deficiency Vit B12 deficiency Liver disease COPD Myelodysplastic syndromes Anaemia from blood loss Normocytic Normochromic Autoimmune haemolytic anaemia SLE Haemoglobinopathies Bone marrow failure Malignancies Anaemia from blood loss Anaemia of chronic disease Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

10. Variations in Definition of Anaemia in pregnancy Non-uniform definition of anaemia in pregnancy WHO 5 : Antenatal Hb < 110 g/L and postnatal < 100 g/L. British Committee for Standards in Haematology guidelines 6 Hb level < 110 g/L in the first trimester Hb < 105 g/L in the second trimester Hb < 100 g/L postpartum period. Nigeria: for practical purposes 100g/L Definition of the severity 5 Mild: Hb 100-109g/L (10.0-10.9g/dl) Moderate: Hb 70-99g/L (7.0-9.9g/dl) Severe: Hb <70g/L ( < 7.0g/dl) Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

11. Fe homeostasis 7,8 Fe re q uired for fetal growth and developm e nt originate s from mother Maternal Fe requirement Decreases in early pregnancy: cessation of menses Increases to up to 3-8mg/day in late pregnancy 0.8mg/day 1 st trimester to7.5mg/d in 3 rd trimester Average re q uirement: 4.4mg/d throughout pregnancy Total body iron requirement for uncomplicated pregnancy: 1000 -1500 mg : fetus/placenta: 350mg ; increase in maternal RBC mass 450mg; bleeding during/after delivery : 250mg . To accommodate these, woman should have 500mg store before, and consume 20mg-48mg dietary iron per day Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

12. Fe deficiency Anaemia (IDA) Refers to anaemia with inadequate serum Iron Causes of deficiency: Inadequate nutritional intake: -Malnutrition -Low socioeconomic status -Vegetarianism -Chronic illness -Malabsorption due to celiac disease Chronic blood loss -Esophageal varices -Bleeding peptic ulcer -Inflammatory bowel disease -Hookworm infestation -Hemorrhoids May be precipitated by increased demand of pregnancy or growth spurt of adolescents Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

13. Folic Acid deficiency Folic acid is a cofactor in nucleic acid synthesis and has important role in cell division. Stores are limited (6-10mg); Daily requirement of 300-500 µ g. Deficiency causes Megaloblastic anemia. Risk factor: Multigravida, twin pregnancy, Hyperemesis gravidarum, alcohol consumption, smoking, malabsorption, antiepileptic drugs. Effects on mother: miscarriage Effects on Fetus: Neural tube defects, Cleft palate, Preterm Birth Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

14. Approach to management Often asymptomatic- incidental finding on routine screening Evidence of Hypoxia: Tiredness, dizziness , fatigue and decreasing capacity to perform daily tasks . There may be pallor, d yspnea , palpitation, headache, lightheadedness (and episodes of fainting), and irritability. General examination: Glossitis, Stomatitis, Koilonychia, pedal edema Systemic examination: Tachycardia, Tachypnea, Basal crepitation if in Heart Failure with third Heart sound Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

15. Screening for Antepartum Anaemia Screening 9 A ssumption that normal Hb implies normal Fe level Aim: Determine aetiology Hb Serum ferritin Iron saturation Total Iron Binding Capacity Reticulocyte count Reticulocyte H b content Folate level Vit B12 level British Society of Haematology 6 recommend s m easure ment of serum Ferritin in women with- Haemoglobinopathy Previous parenteral Fe therapy Previous anaemia Multiparity I nter-pregnancy interval <1 year Teenage pregnancy Recent bleeding episode High risk of bleeding in index pregnancy Jehovah witnesses or vegetarians Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

16. Diagnosis of Fe deficiency in pregnancy 9 Serum ferritin : most widely used laboratory t est Ferritin is an intracellular protein found at a number of sites (e.g. liver & spleen ) which store and release iron in a controlled fashion. S mall quantities of ferritin present in human serum. Serum ferritin level can assess body’s total iron storage Note: F erritin is an acute phase protein and increases during active inflammation , malaria . Most Physicians use: cut off value of < 30 μg /L. The threshold has 90% sensitivity and 85% specificity for detecting iron deficiency during pregnancy Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

17. Laboratory testing Hb: booking, 28weeks Red cell indices -Low Hb, MCV, MCH, MCHC: suggest Fe deficiency note: MCV rise in pregnancy (6fl) -Serum Fe reduces in pregnancy: 12 µmol/L and TIBC<50µmol/L indicate Fe deficiency Another study 10 reported that MCHC most sensitive in early prediction of IDA: this needs further validation Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

18. Laboratory testing- 2 Peripheral blood smear – microcytosis , hypochromia , anisocytosis , poikilocytosis and target cells RBC indices: ↓ MCV, ↓MCH, ↓MCHC, MCV is the most sensitive indicator ↓ Serum ferritin – first abnormal laboratory test ↓ Transferrin saturation – second to be affected ↑ Serum transferrin receptor – best indicator Bone marrow examination – no response to treatment after 4 weeks of therapy Stool examination – for three consecutive days Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

19. Co mplications of anaemia in pregnancy Foetal S tillbirth, Placenta Abruptio n Fe status compromised with Maternal Hb < 85g/ L, Ferritin < 13.4 µ g/L Maternal Preterm labour,↑ intervent i on during labour including CS, ↑Risk for PPH, maternal death, postpartum depression, altered maternal-infant bonding, ↑blood transfusion Neonates: LBW & increased NICU admission A naemia, neurodevelopmental disorders - low IQ score, poor school performance, visual & motor coordination defects , subnormal language development. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

20. General Approach 12 - RCOG Screen at booking, then 28 weeks Normocytic or microcytic anaemia: oral iron, check for rise at 2 weeks ( assess compliance ) . Parenteral iron is indicated with no response Provide information on dietary advice Encourage hospital delivery Active management of third stage of labour to minimize blood loss Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

21. Oral Fe Oral Fe is t he first‐line treatment for IDA in pregnancy O ral dose of iron is 100–200 mg of elemental iron daily. Ferrous salts can be taken on an empty stomach to increase absorption I ron polymaltose preparations can be taken with food. C hallenges of c ompliance : GI side effects ( nausea, diarrhoea , constipation. E xpected rise in Hb is 10 g/L over a two‐week period. If response is adequate , continue maintenance therapy u ntil delivery. Take with water or a source of Vit C, preferably in the morning (lowest hepcidin level), avoid concomitatnt use with antacid or multivitamin. >80mg elemental iron per day increases GI side effect Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

22. Parenteral Fe P oor / absent response to oral iron (Hb rise <10 g/L within 14–28 days ) L ack of compliance or intolerance to oral iron S evere anaemia (Hb <80 g/L) with no symptoms or need for immediate transfusion N eed for timely and rapid treatment in the 3rd trimester W omen at high risk for major bleeding (e.g. placenta previa). IV iron offers earlier replenishment of total body iron stores / timely increase in Hb Available IV iron preparations : I ron sucrose, I ron gluconate, low molecular weight iron dextran, ferric carboxymaltose, iron polymaltose complex , iron isomaltoside, and ferumoxytol Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

23. Safety profile of IV Fe Acute severe reaction-uncommon Doses administered are insufficient for parenchymal damage Increased risk for infection and CVS diseases- unproven Initially bioactive free iron, now Fe-CHO complexes reduced toxicity Commonest formulations : Ferrous Carboxymaltose , Fe Isomaltoside, Ferumoxytol : Rapid infusion, no premedication, a dverse effects are uncommon Contraindication: Previous anaphylaxis to parenteral Fe, decompensated liver disease 6 Hypophosphatemia after IV Fe: (especially FCM)- ongoing research in Nigeria (IVON Trial- Prof Afolabi et al) Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

24. Parenteral Fe (contd) Calculating Iron deficit Elemental iron needed (mg) = [(Desired Hb – Patient’s Hb)g/L x Weight (kg) x 0.24] +50% (to replenish the store) Fe C arboxymaltose : given IV, comes in 50mg/ml formulation, dilute in 200ml N/S, no need for test dose, no premedication, can be given over 15-20minutes, maximum dose in 1000mg. See manufacturer’s brochure Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

25. Assessing response to therapy Sense of well being Improved outlook of patient Increased appetite ↑ Hb: 2 weeks after commencement Reticulocytosis within 5-10 days If no significant clinical or haematological improvement in 3 weeks, Re-evaluate Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

26. Indications for blood transfusion Severe anaemia with severe symptoms (Hb<7g/dl) Acute blood loss with continuing bleeding Women at risk for additional bleeding Imminent cardiac compromise Severe anaemia beyond 36 weeks Refractory anaemia Non-response to Iron therapy Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

27. Blood transfusion cases General recommendations: Compatible, screened, cross-matched, no TTI Packed cells preferred over 4-6 hours and given alternate days For acute blood loss, replacement may be faster End point: Hb 9g/L before 34 weeks and 11g/L after 36 weeks Prophylaxis against infection in severe anaemia: ↓low resistance to infection or actual infection Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

28. Peripartum management First stage Make Comfortable, Avoid maternal stress, Analgesia Partograph Adequate oxygenation Avoid sympathetic stimulation & hyperventilation: rightward shift of ODC Improve uterine blood flow Second stage: Shorten (forceps) Third stage Active management of third stage, Prophylaxis for PPH Puerperium Adequate rest Iron & folate therapy for 3/12 Sepsis: Prophylaxis, watch out and treat early Others: failure of lactation Uterine sub involution Thromboembolism Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

29. Postpartum anaemia There is lack of consensus on the definition of postpartum anaemia WHO: Hb <100g/L USA ( CDC ): Hb <118 g/L 13 The RCOG and the British Committee for Standards in Haematolo gy 6 : Hb <100 g/L The Swiss Society of Gynaecologists and Obstetrics 15 : Hb <120 g/L. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

30. Screening for PP Anaemia 9 Universal versus selective screening S elective testing : no reliable, validated risk assessment screening tools and the estimation of blood loss associated with delivery is often inaccurate. The optimal time point for testing is controversial (6-48 hours) There are complex hormonal, hemodynamic and haematinic changes that occur in postpartum period and after a normal delivery it may take 5–7 days for the maternal extracellular and intravascular changes to reach equilibrium. Earlier testing : significant PPH and/or uncorrected antenatal anaemia . If anaemia is detected, assess body iron status to confirm Fe deficiency. Note: There is oxidative stress / inflammatory respons e; elevated ferritin levels may be present for up to one week postpartum. E xpert opinion : suggests use of Ferritin after the first week postpartum Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

31. Screening & Management of Postpartum Anaemia Definition Swiss Society for Gynae & Obs 15 Expert Committee for Asia-Pacific Region 16 Network for Advancement of Patient Blood Management, Haemostasis &Thrombosis ( NATA) Guideline 17 Definition (Hb) <120 g/L <100g/L <100g/L within 24-48 hours Oral Fe Rx Treat when Hb 95-120 g/L Hb 95-99g/L start 24-48hr PP Asymptomatic/ mild symptom Mild-moderate anaemia IV Fe Rx Hb 85-95g/L Hb 65-95g/L Start 24-48hr PP No response to oral Fe (2-4wks) Intolerant of Oral Fe Blood transfusion Hb <60-65g/L Hb <65 g/L Unstable: cardiovascular Poor response to IV Fe At risk from IV iron Hb <60 g/L (non-bleeding patient) taking clinical signs and symptoms into consideration. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

32. Recommendation: NATA in conjunction with FIGO and EBCOG Screen for anaemia at booking, 28weeks, or any time if symptoms of anaemia are present Microcytic or normocytic anaemia from ID: confirm by a trial of oral iron (unless Haemoglobinopathies) or a serum ferritin Poor response to oral Fe: Serum ferritin plus other evaluation Anaemic women (Mediterranean, Middle/ Far East or Africa): r/o Haemoglobinopathies Anaemia in known haemoglobinopathy: serum ferritin check (give oral Fe only if <30 ng/mL). Areas with a high prevalence of anaemia in pregnancy: Routine daily oral iron (30–60mg) and folic acid (400 𝜇g) Mild-moderate IDA (Hb≥80 g L) in 1st/2nd trimester: oral iron + folic acid Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

33. Recommendation: NATA in conjunction with FIGO and EBCOG- 2 Once the Hb is in the normal range, continue Fe supplementation for at least 3months to replenish iron stores Consider IV Fe: severe IDA (Hb <80 g /L), IDA after 34 weeks of gestation Consider IV Fe: women with confirmed IDA who fail to respond to oral iron (Hb increase <10 or 20 g/L in 2-4 weeks) or intolerant to oral Fe Give erythropoiesis stimulating agents (ESA): moderate-severe anaemia not responding to IV Fe due to inappropriate synthesis of, and/or response to, endogenous erythropoietin levels, in consultation with a haematologist Make every effort to correct anaemia prior to delivery + Hospital delivery Active management of the 3rd stage of labour to ↓ blood loss Mild-Moderate PPA: Give 80–100mg elemental Fe daily for 3 months if haemodynamically stable and asymptomatic or mildly symptomatic Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

34. Knowledge Gap/ Research Opportunities 1. Methods of Diagnosis (Hb measurement) 18 Detailed cost-analysis of accurate tests Method Sensitivity (95% CI) Specificity (95%CI) Clinical Assessment 56% (19-92) 62% (30-93) Haemoglobin colour scale 67% (56-76) 67 %(48-82) Cu sulphate test 97% (88-100) 71% (55-85) Sahli 86% (75-94% 83% (68-93) Hemocue 85% (79-90) 80% (76-83) N on-invasive Hb sensor (HBM 2000) 34% (27-41) 92 (82-97) Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

35. 2. Hb Cut-off to define Anaemia Universal vs. Locality cut-off : E thnicity /geography GA-related cut-off Maternal age specific cut-off GA Specific Cut-off Based on the non-linear relationship of Hb with GA China 19 : 143,307 singleton pregnancies, 139 hospitals Mean Hb: 125.75g/L (T1), 118.71g/L (T3 ) Reference for anaemia: T1 : 108g/L ; T2: 103g/L; T3 : 99g/L Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

36. 3. D aily iron and folic acid supplementation WHO recommendation 20 Fe: 30-60mg elemental Fe + Folic acid: 400µg (0.4mg) Randomized double-blind, intention-to-treat study comparing 20mg, 40mg, 60mg, 80mg oral Fe fumarate (comparable groups) 21 Serial Evaluation with Fe st a tu s markers (Hb, serum ferritin, soluble transferrin receptors) at 18/52, 32/52, 39/52 GA ; 8/52 PP 20mg group- ↓parameters at 32/52, 39/52 No significant difference b et w een 40mg, 60mg & 80mg Side effects: not sig nificant in all 4 groups 40mg is appropriate for supplementation 30 mg elemental Fe ( 150mg Fe SO4 , 90mg Fe fumarate or 250mg Fe gluconate ) Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

37. 4. Dosing regimen 22 Non-inferiority study of dosing for oral iron Thrice weekly (TIW) vs. daily dosing (TID) Primary outcom e: ↑Hb ≥3g/dl Secondary: Adverse effect, RBC indices, Fe profile, compliance Recovery of TID more rapid but ALL participants had recovered by 4 weeks of study No statistical difference in Biomarkers assessed TIW is not inferior to TID TIW fewer GI adverse effect, lower cost Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

38. Haemoglobinopathies Haemoglobinopathies are conditions in which there is an inherent haemoglobin defect resulting in abnormal (e.g. sickle cell) or reduced globin formation (e.g. thalassemia) SCD is commoner: autosomal recessive disorder characterised by abnormal Hb genotype with occurrence of Sickle cell haemoglobin (Hb S ) in combination with another abnormal Hb The genes for inheritance are transmitted in the Mendelian fashion, so both homozygous and heterozygous forms occur Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

39. Haemoglobinopathies-2 Characterized by sickling of RBC during physiological stress leading to vaso-occlusion with pain crises, but can cause more serious complications. SCD leads to ↑ red cell turnover and a chronic haemolytic anaemia which is further affected by the physiological changes of pregnancy. The most common forms of SCD are: - HbSS; HbSC; HbS β-thalassaemia. More rarely there are other causes of sickle cell disease: - HbSD-Punjab; HbSE; HbSO-Arab. HbSC: ↓ complications; but ↑Pain crises, IUGR, Antenatal Hospitalization, PP Infection, requires same level of vigilance as HbSS Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

40. Haemoglobin Hb S : V aline replaces Glutamic acid at position 6 of the β globin chain Hb C : lysine replaces glutami c acid at postion 6 of beta chain T halassaemias : reduction in the synthesis of either alpha or beta chain H b is a polypeptide with MW 64450, the oxygen carrying pigment in the RBC Made up of 4 subunits, each subunit contains heme moiety conjugated to a polypeptide Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

41. PATHOPHYSIOLOGY Deoxygenation causes valine to form hydrophobic bonds with adjacent globin chains with insoluble tetramas,which polymerises into long fragile and rigid strands that deform the red cell membrane and block small vessels causing pain crises . This phenomenon is known as sickling and it is aggravated by an increased concentration of HbS within the RBC, infection, acidosis, dehydration, hypoxic state, extreme change of temprature and stressful conditions including pregnancy. These cells are prone to increased breakdown, which causes haemolytic anaemia Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

42. CLINICAL FEATURES Associated with 2 major crises Anaemia : increased haemolysis, aplastic / sequestration crises Pain crises : ischaemia from vaso-occlusion of micro vasculature Other clinical features Sickle cell faci e Avascular necrosis of the head of femur ( common in HbSC ) Pelvic deformities Subfertility and Infertility ; reproductive career may be marred by high incidence of fetal loss. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

43. INVESTIGATIONS Sickling test ; Solubility test Haemoglobin electrophoresis. Full Blood Count and Blood Film Serum Ferritin, serum iron and TIBC Serum folate assay Urinalysis Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

44. Complications of SCD Maternal Complications Worsening anaemia Increased risk of infections, particularly UTI and chest infection Increased sickle cell crises, particularly in the third trimester Acute Chest syndrome Hypertension and pre-Eclampsia Thromboembolic disease Foetal Inheritance of HbS gene Miscarriage IUGR IUFD Preterm delivery Stillbirth Opiate toxicity in neonate Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

45. PRE-CONCEPTION CARE Aim: To optimize the woman Should plan their pregnancies and offered pre-conception care by MDT D iscuss risks related to pregnancy -Drug review ( potential teratogenic ity)- D/C Hydroxycarbamide at least 3 months before pregnancy ( not an indication for termination ); ACE inhibitors , Angiotensin II receptor blockers, Hydroxyurea and chelation therapy . -Ensure Folic acid and Prophylaxis with Proguanil -Pain management: PCM, Codeine, NSAID, Opioid -Penicillin prophylaxis: encapsulated bacteria e.g. (N meningitidis, Strep pneumonia, H influenza) Perform G enetic screening / partner testing : appropriateness of PGD, NIPT Vitamin D deficiency is common - Regular monitoring and su pplementation History & Physical examination Pre-conception review of chronic complications of SCD: Renal, HTN, CVA, AVN Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

46. Antenatal care MDT: Obstetrician, Haematologist, Midwives, counsellor Revisit Prenatal care Genetic screening: prenatal test Appointment: Individualize, Monitor- Hb, BP, Urinalysis, etc. Fe supplementation: only for proven deficiency Report & treat Hyperemesis promptly Multiple gestation: higher risk, closer monitoring PIH: Higher risk Aspirin prophylaxis from 12 weeks Risk assessment for VTE +/- Prophylaxis Serial USS: 1st trimester, 20, 24 weeks then every 4 weeks 36 weeks: Review Birth plan Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

47. Blood transfusion 24-26 Consider in: worsening anaemia, acute SCD complications , Women on long-term transfusion for stroke prevention or to ameliorate severe SCD complications should continue throughout pregnancy Standard care vs. Prophylactic Meta-analysis on prophylactic transfusion 25 : ↓VOC, Preterm delivery, maternal/ perinatal mortality, neonatal death. No difference: UTI, PE, Acute chest syndrome, SGA, LBW, IUFD When?- Poor Clinical status, Complications (ACS, Intractable pain), Hb<60g/L Optimal Hb before CS: Inconclusive, (Hb >90g/L ↓ post-op sickle complications [ACS]) 26 Give ABO-compatible, Rh, Kell and CMV Negative, Matched blood. If woman had significant Red cell antibodies, give blood without the corresponding antigens Consider prophylactic transfusion: Previous or current medical, obstetric or fetal problems related to SCD Women on hydroxycarbamide before pregnancy Multiple gestation Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

48. Acute Pain Crises Commonest complication in pregnancy ↑Antenatal and postpartum period for HbSS Why? -Physical/Psychological stress, dehydration, worsening anaemia, ↑Red Cell turnover, pro-coagulant state of pregnancy, ↑Infection risk Mild: rest at home, oral fluids, PCM, weak opioids, NSAID. Severe: MDC, Admission, IVF (caution in Renal Disease, PE), Opioid, (Avoid Pethidine- Associated seizure), Oxygen- keep SPO2>95%, precipitating factor, Antibiotics- infections, Thromboprophylaxis (LMW Heparin), +/-Blood transfusion Monitor with pain score; ICU care if no improvement. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

49. Acute Chest Syndrome Life threatening complication, occurs in 10% of women May develop before or after admission for other reasons Fever and/or respiratory symptoms, hypoxia FBC, Chest x-ray (pulmonary infiltrates), Arterial blood gases Precipitated usually by infection: search for the focus Pain relief, rehydration, Spirometry, treat infection (bacteria or viral), Blood transfusion especially in hypoxic women (simple or exchange transfusion) Critical team care: ICU care If blood transfusion is necessitated, may need prophylactic transfusion for the rest of the pregnancy. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

50. Venous Thromboembolism (VTE) and Thromboprophylaxis SCD increases risk for VTE and DVT during pregnancy and Puerperium VTE risk 3-5 in women with complications: VOC, etc. Risk assessment: early pregnancy, if admitted, Intrapartum, postpartum periods Thromboprophylaxis from 28weeks till 6weeks PP, If there are additional risk factors, start from beginning of pregnancy Offer Thromboprophylaxis for VOC or other pain crises Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

51. Labour and Delivery When to deliver: If pregnancy is uncomplicated, delivery should be planned for 38 to 40 weeks Mode of delivery: will be determined by obstetric factors, no contraindication to VBAC Delivery at a facility with MDT and can manage probable complications Optimal Intrapartum care: -Avoid hypothermia- Keep warm -Avoid hypoxia: Oxygen supplementation -Adequate hydration -Adequate analgesia: Epidural is preferred -Avoid prolonged labour (>12 hours)- Partograph -Antibiotics- low threshold -Available grouped/crossmatched blood: 2 units of compatible Hb AA blood -Continuous electronic fetal monitoring -Serial Hb and Urinalysis -Shorten second stage of labour In unplanned delivery/emergency, reverse heparinisation using protamine sulphate when the second stage of labour is imminent or immediately before an operative delivery Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

52. Postpartum care Remain vigilant: (20-25% crises are postnatal) Maintain hydration, oxygenation, analgesia Early ambulation Other routine care including breastfeeding If baby is at higher risk of SCD, send samples to laboratory with facilities for early diagnosis Antithrombotic stockings Thromboprophylaxis- up to six weeks Contraception: Individualize, Progestagen-only methods reduce risk of sickle pain crises. Barrier method, Sterilization, IUS can be used. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

53. Thalassemia Group of inherited blood disorders with abnormal formation of RBC Women may be transfusion dependent or non-transfusion dependent Transfusion dependent women need their medical care optimized before pregnancy where possible as this can be associated with organ damage due to iron overload (cardiac disease, diabetes). This can lead to increased risks to the mother and safety of pregnancy should be considered. Iron chelation should be reviewed, and where possible, stopped 3 months pre- conception. Non-transfusion dependent women may require transfusion support in pregnancy due to the physiological changes which occur and so should be monitored by a specialist team. Most other care similar to SCD Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

54. CONCLUSION In view of the common nature of anaemia in pregnancy, facilities should have protocols for the management. Since most Haemoglobinopathies are inherited as autosomal recessive disorders, screening counselling and prenatal diagnosis are important Social support for these women is mandatory, as the diseases is a major drain on their emotional, physical and financial reserves. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

55. References 1. Adeniran AS, Ocheke A.N, Nwachukwu D, Adewole N, Ageda B, Onile T, et al. Non-obstetric causes of severe maternal complications: a secondary analysis of the Nigeria Near-Miss and Maternal Death Survey. BJOG. 2019;126 (3):41-48. 2. McLean E, et al. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009;12(4): 444-454. 3. Fite MB, Assefa N, Mengiste B. Prevalence and determinants of anaemia among pregnant women in sub-Saharan Africa: A systematic review and Meta-Analysis. Arch Public Health. 2021;79(1):219. 4. Ezechi O, Kalejiye O. Management of Anaemia in pregnancy. Chapter in a Book. DOI: 10.5772/28646. 5. WHO: World Health Organization. Haemoglobin concentrations for the diagnosis of anemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Department of Reproductive Health and Research, WHO,Geneva;2011.https://apps.who.int/iris/bitstream/handle/10665/85839/WHO_NMH_NHD_MNM_11.1_eng.pdf. Accessed March 1, 2021. 6. Pavord S, Myers B, Robinson S, Allard S, Strong J, Oppenheimer C. British Committee for Standards in Haematology. UK guidelines on the management of iron deficiency in pregnancy. Br. J. Haematol. 2012;156(1):588–600. 7. Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am. J. Clin. Nutr. 2000; 72: 257S–264S. 8. Milman N. Iron prophylaxis in pregnancy–general or individual and in which dose? Ann Hematol. 2006;85:821–828. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

56. References- 2 9. Butwik AJ, McDonnell N. Antepartum and Postpartum Anaemia: A Narrative review. Int J Obstset Anaestet 2021;102985 10. Rabindrakumar MSK, Pujitha WV, Gooneratne L, Arambepola C, Senanayake H, Thoradeniya T. The role of haematological indices in predicting early iron deficiency among pregnant women in an urban area of Sri Lanka. BMC Hematology. 2018;18(1):37. 11. Wiesenack C, Meybohm P, Neef V, Kranke P. Current concepts in preoperative anaemia management in obstetrics. Curr Opinion Anaes. 2023;36:255-262. 12. RCOG. Blood transfusion in obstetrics. Green Top Guideline No. 47. May 2015. 13. Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR Recomm Rep. 1998;47(1):1–29. 14. Breymann C, Honegger C, Hösli I, Surbek D. Diagnosis and treatment of iron deficiency anaemia in pregnancy and postpartum. Arch Gynecol Obstet. 2017;296(54):1229–1234. 15. Breymann C, Bian XM, Blanco-Capito LR, Chong C, Mahmud G, Rehman R. Expert recommendations for the diagnosis and treatment of iron-deficiency anemia during pregnancy and the postpartum period in the Asia-Pacific region. J Perinat Med. 2011;39:113–121. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

57. References- 3 16. Munoz M, Pena-Rosas JP, Robinson S, Milman N, Holzgreve W, Breymann C, et al. Patient blood management in obstetrics: management of anaemia and haematinic deficiencies in pregnancy and in the post-partum period: NATA consensus statement. Transfus Med. 2018;28:22-39. 17. Sobhy S, Rogosinska E, Khan KS. Accuracy of on-site tests to detect anaemia during prenatal care. Int J Obstet Gynecol.12289 18. Sun M, Gu T, Wu T, Gong X, Li X, Huang J, et al . Variation Patterns of Hemoglobin Levels by Gestational Age during Pregnancy: A Cross-Sectional Analysis of a Multi-Centre Retrospective Cohort Study in China. Nutrients. 2023 ; 15 : 1383. 19. WHO. Guideline: Daily iron and folic acid supplementation in pregnant women. WHO Geneva, 2012. 20. Milman N, Bergholt T, Eriksen L, Byg K, Graudal N, Pedersen P, et al. iron prophylaxis during pregnancy- How much iron is needed? A randomized dose-response study of 20-80mg ferrous iron daily in pregnant women. Acta Obstet Gynecol Scand. 2005;84:238-247. 21. Siddhibhong J, Thitima D, Warunsuda S, ArnuparpL. A randomized controlled trial of thrice-weekly versus thrice-daily oral ferrous fumarate in adult patients with iron-deficiency anaemia. Ann. Hematol. 2023;102:1333–1340 Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

58. References- 4 23. NHS. Haemoglobinopathies in Pregnancy: Guideline for Management. Trust Ref: C74/2006 Approved by: Maternity Service Governance Group: April 2022 24. Oteng-Ntim E, Pavord S, Howard R, Robinson S, Oakley L, Mackillop L, et al on behalf of the British Society for Haematology Guidelines Committee. Management of sickle cell disease in pregnancy: A British Society for Haematology Guideline. Br J Haem 2021;194:980-995. 25.Malinowski AK, Shehata N, D’Souza R, Kuo KH, Ward R, Shah PS, et al. Prophylactic transfusion for pregnant women with sickle cell disease: a systematic review and meta-analysis. Blood. 2015; 126: 2424–35. 26.Howard J, Malfroy M, Llewelyn C, Choo L, Hodge R, Johnson T, et al. The Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS) study: a randomized controlled multi-centre clinical trial. Lancet. 2013;381:930–8. Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023

59. Thank you for listening Anaemia & Haemoglobinopathies in Pregnancy UPDATE Course July 2023