ANAEMIA IN PREGNANCY

INTRODUCTION

• Most common pregnancy complication worldwide

• > 50% of all pregnant women in developing countries affected.

• In Africa Prevalence estimate 50 – 60%

• Tanzania, DSM at booking for ANC 60% anaemic, 4% severely anaemic ( Massawe at el 2002).

• Contributes significantly as an indirect cause maternal deaths in developing countries.

• Most common anaemia during pregnancy is Iron deficiency.

DEFINITION•WHO, Hb < 11g/dl or Hct < 0.33.

•In Africa Hb< 10g/dl or Hct < 0.30, 2nd

trimester.

•Moderate anemia with Hb >7.0g/dl

•Severe anaemia with Hb< 7.0g/dl.

•Very severe anaemia Hb < 4.0g/dl

Anemia: Etiologies

• Inadequate dietary intake

• Poor nutrition • Chronic alcoholism• Decreased consumption

of animal protein and ascorbic acid

• Inadequate GIT absorption

•Malabsorption syndromes•Certain drugs/foods

• Increased iron demands

• Multiparity

• Diarrhea, HIV/ AIDS and

• UTI

• Recurrent Infections-Tuberculosis, Amoebiasis , Giardiasis, Roundworm

• other infectious diseases

•Blood loss• Hookworm infestation• Malaria • Bleeding piles &gums • Surgery• Gastrointestinal bleeding• Trauma• Dialysis

HAEMODILUTIONAL/ PHYSIOLOGICAL ANAEMIA:

• In pregnancy, increased demand for nutrients as a result of the expanding RBC mass, fetus and placenta.

• Fall Hb level in healthy pregnant women not deficient in Fe/FA is due to a relatively higher increase in plasma volume as compared to RBC mass.

• Maternal blood volume starts to increase during the 1st trimester, expands most rapidly during the 2nd trimester, rises at much slower rate during the 3rd trimester, plateau during the last several weeks of preg.

• Maternal Blood volume increases markedly during preg. At term 40 –45% of non pregnant volume.

• Like wise serum transferrin rises quite markedly right from the first trimester.

•Cause of the increase in blood volume is mainly hormonal, both aldosterone and oestrogen increase markedly in preg.

• These cause an increase in salt and water retention by the kidneys.

•Oestrogen – secreted by the placenta.

•Aldosterone – partly due to relative hyponatraemia resulting from maternal Na utilized by the growing fetus.

Pregnancy induced hypervolaemia:

1. Meet demands of enlarged uterus with greatly hypertrophied vascular system.

2. Protect mother and fetus from the deleterious effects of impaired venous return in supine and erect positions.

3. Safeguard the mother from the effects of blood loss associated with parturition.

IRON DEFICIENCY

• The most common – 95%

May result from:

(a) Inadequate intake of Fe /low dietary availability.

(b) Increased Fe needs during preg.

(c) Periods of rapid growth e.g. adolescence.

(d) hookworms, schistosomiasis.

(e) Impaired Fe utilization in chronic and repeated infections.

• Staple diets which consist of cereals, legumes and vegetables lack the advantage of mixed diets. The non haem Fe they contain in abundance is of vegetable origin, poorly absorbed.

• Other constituents e.g. Tannins (in legumes, coffee and tea) polyphenols, phytates (in cereals) and vegetable proteins inhibit Fe absorption.

Anaemia develops rapidly because in many cases Fe stores are depleted even before

pregnancy starts.

Demand for Iron.• The additional Fe demand during preg. is 1000mg:

450mg• for expansion of RBC mass and increase in blood volume

300mg• for the fetus

200mg• for continuing maternal basal losses: gut, urine , skin

50mg• for the placenta

•Almost all the iron for these purposes is used during the later half of preg.

• In absence of added exogenous sources Hb conc. Fall rapidly as maternal blood volume increases rapidly.

•Hb production in the fetus will not be affected because the placenta obtains iron from the mother in amounts sufficient for the fetus to establish normal Hb levels even when mother has severe anaemia.

Facts about Iron loss and gain

• After delivery part of the Fe in some of these organs returns to maternal storage sites in the bone marrow.

• Fe in the fetus, placenta and blood shed during delivery is lost.

• Post partum loss averages 150mg in normal SVD, about 300mg in C/S.

• Savings from pregnancy amenorrhoea don’t exceed 1mg daily.

• A non preg woman absorbs about 2mg/day of Fe from her diet in order to maintain adequate Fe balance,

• Demands in preg increase to 3mg/day in 2nd trimester and to 5mg/day in the 3rd.

• The requirements are easily met and Fe deficiency avoided by a mixed diet, rich in ‘haem Fe’ which is readily absorbed, also contain animal protein and vit c both enhance Fe absorption.

Iron DeficiencyHaematological Findings:

• Hypochromic, microcytic

• Anisocytosis and poikilocytosis are marked.

• Target sign – central pallor

• Low MCV, MCH, MCHC

• Bone marrow: normoblastic erythropoiesis, stainable Fe absent from reticulum cells.

• Serum ferritin and transferrin low.

• Total iron binding capacity is high

Folate deficiency• Important in cell division and nucleic acid synthesis. Thus demands in preg

increase markedly.

• Requirements per day, 400ug in non-preg state,

rises to 800ug in pregnancy.

• Deficiencies common in multigravidae, twin preg, Last trimester and lactation.

• Dietary inadequacy leads to negative folate balance this results in deficient haemopoiesis.

• Bone marrow becomes megaloblastic and anaemia worsens.

• FA is thermolabile and water soluble, overboiling and overstewing greatly reduces FA available in food. Endemic malaria and presence of some haemoglobinopathies exacebate negative folate balance.

•Haematological findings in FA deficiency:

(i) Normochromic, macrocytosis

(ii) Poikilocytosis anisocytosis

(iii) Increase in proportion of multilobed polymoprhs to >4%.

(iv) Reticulocytosis and raised bilirubin levels.

(v) Megaloblasts – in florid cases.

(vi) Pancytopenia (bone marrow arrest) - rare

Combined Fe and Folate deficiency

•Dimorphic anaemia with peripheral blood smear shows both Fe and Folate def.

•Occurs where nutritional standards are particularly low.

Vit. B12 Deficiency

• Rare

• Essential for cell division, demand increase during preg.

• Animal products main source.

• Unlike Folate, stores in liver last longer, up to 2 yrs.

• Daily req. so low 3ug in preg.

• Causes:

-Lack/def. Of IF, atrophic gastritis, gastrectomy.

-Malabsorption syndrome

-Increased demand.

Clinical Features:

•Nervous manifestations

- Sub acute combined degeneration of the spinal cord.

- Peripheral neuritis.

•Anemia due to B12 def: the smear picture is like that of falate deficiency.

Malaria • Increased susceptibility to malaria in preg. Esp. prim and 1st

half of preg

• Many asymptomatic, main effect seen, anaemia.

• Haemolysis caused raise FA requirements.

• Preexisting Fe & folate def. Can exacerbate anaemia due to malaria and viversa.

• Anaemia due to malaria follows repeated falciparum parasitaemia, its features in partially immune and non-immune differ.

PARTIALLY IMMUNE WOMEN:

• Anaemia starts in 2nd trimester of preg.

• Commonly btn 16th and 24th wks of GA.

• Young & prim >> older & multigravida

• Principal cause: immune mech. Triggered by malaria parasitaemia.

-haemolysis, parasitized&non-parasitized RBCs.

-Sequestration of para & non parasitized RBCs.

-Dyserythropoiesis.

• Severity of anaemia and degree of parasitaemia don’t match.

• Causal immune mechanisms may continue for months after parasitaemia and may require steroids.

NON-IMMUNE WOMEN:

• Anaemia can complicate a severe malaria attack at any stage pregnancy.

• No parity difference.

• Acute haemolysis, impared marrow fn, 2ndary bacterial infection involved.

• Degree of anaemia correlates well with level of parasitaemia.

• Thrombocytopaenia is common.

• Dx, malaria pigment in monocytes in stained blood film.

Hookworm infestation• Endemic in many tropical countries.

• Blood loss caused contributes to anaemia.

• Both, N. americanus & A. duodenale.

• Adult forms – human intestines

• Ova & larva soil contaminated with feces.

• Both spp. 1000ova/g feces, loss of 1mg Fe per day.

• Degree of anaemia depends on

- content and bioavailability of iron in diet,

- amount of body iron stores,

- duration of infestation,

- intensity of infestation.

• Dx: stool microscopy, hookworm ova.

• Schisto may contribute, alone no severe anaemia.

Haemorrhage • Usually encountered in the first trimester.

• APH cause serious anaemia before and after delivery.

• Acute blood loss early in preg occurs due to an ectopic preg, abortion or hydatidiform mole.

• Advanced abdominal preg is often xrized by severe anaemia.

• Postpartum haemorrhage an important cause of morbidity in pueperium.

Haemoglobinopathies

•That cause anaemia in preg include:

-Sickle cell disease

-Thalassaemia

-Homozygous Haemoglobin C

-Haemoglobin H disease

•Mainly haemolytic, folate def. A feature.

Sickle cell disease• Autosomal inherited disorder.

• Manifestations appear in homozygous not heterozygous.

• Glut. Acid in position 6 of b-chain of Hb molecule replaced by valine =HbS.

• HbS on exposure to hypoxia forms insoluble aggregations and RBCs become sickle shaped subsequently fragment.

• In addition the sickle shaped cells increase blood viscosity, occlude blood vessels of various organs.

• Anaemia during preg is frequent and may be severe.

• Ongoing red cell haemolysis adds more to the folate demand.

• If dietary folate is low and not supplemented, bone marrow becomes megaloblastic followed by worsening anaemia.

• When P.falciparum is endemic, parasitaemia increases during preg.

• The RBC haemolysis from SCD itself and from malaria combine to increase the folate demand and add to the risk of anaemia.

• Besides haemolysis and folate def. other causes of anaemia :

-Acute sequestration crises

- Aplastic crises.

Acute sequestration crises:

•More common in HBSc and HbSb-Thalassaemiathan HbSS.

•What triggers the crisis is not known.

•Can occur any time during preg, labour and pueperium.

• It’s effects are strikingly dangerous during labour so that death within 2 hours is not unsual.

Aplastic crises:•Occurs during epidemics of upper resp. tract illness

caused by Parvovirus infection.• Erythropoiesis fails, reticulocyte count drops from 10

to 0.5%.•WBC count, platelet count and serum bilirubin remain

unchanged and spontaneous recovery occurs often.• This particular complication of SCD is largely a

paediatric problem so adolscent pregnant girls with SCD may be affected.

Thalassaemia

• An autosomal dominant disorder resulting from failure of production of either alpha-chain(a-Thalassaemia) or beta-chain (b-thalassaemia) of Hb molecule and their replacement with other polypeptide chains.

• a-thalassaemia minor(heterozygous)

- Pt develop mild progressive anaemia during preg.

• B-thalassaemia major(homozygous)

- Rarely encountered in preg. Women but if it happens the prog. Is poor.

Effect on preg: anaemia becomes severe in mid preg and may result in heart failure.

Bacterial Infections

• Immune status is altered during preg. Thus predisposed to various infections.

• Both chronic and acute bacterial infections may be responsible for anaemia when severe /prolonged, particularly with abscess formation, sepsis, TB, etc

• Interfere with nutrient uptake and depress bonemarrow activity resulting in anaemia.

• Also comes from combined effects of various immunological and haematological disturbances induced by fever and bacterial toxins.

• Where severe bacterial infection and anaemia coexist they are mutually aggravating and ineffective to treat one without treating the other.

HIV/AIDS

• In sub-Saharan Africa the prevalence is increasing in women of reproductive age.

•Opportunistic infections and dietary def. in AIDS pts is associated with anaemia.

•Diminishes the preg women’s capacity to control P.falciparum infection, increasing risk of anaemia.

Thrombocytopaenia

In preg may appear clinically idiopathic or more often to be associated with one of the following:

• Acquired hemolytic anaemia

• Severe Preeclampsia/ eclampsia.

• Severe obstetric haemorrhage with blood transfusions

• Consumptive coagulopathy from placenta abruption or similar hypofibrinogenic states.

• Septicaemia.

• Lupus erythematosis

• Antiphospholipids antibodies

• Megaloblastic anaemia caused by severe folate def.

• Drugs

• Viral infections

• Allergies

• Aplastic anaemia or excessive irradiation

Miscellaneous obstetric factors:

• Anaemia disproportionately affects teenage primigravidas, highly parous women and those with multiple pregnacies.

• Socio-economic deprivation and traditional practices:

Teenagers:

• low status in the society

• poor antenatal care

• Poor naurishment

• Increased vulnerability to malaria

Highly parous women:• Too many preg closely spaced = high nutritional demand.

• No time for physiological recovery after preg and lactation.

Socio-economic deprivation and traditional practices:

• Low nutrient intake

• Non use of health services

• Female oppressive traditions

• Food taboos imposed on preg. women, often placing more restrictions to animal derived products and fresh vegetables than on carbohydrates resulting in exclusion of protective nutrients from the diet.

CLINICAL FEATURES

Correlate with severity:

Moderate, severe and very severe anaemia.

• Moderate anaemia (Hb >7g/dl, Hct: 0.20):

- may not have any symptom

- Effect of low Hb compensated for by increase in O2 release to tissues, that sxspecific to anaemia - minimal.

- Clinical features of an underlying disease may be present: malaria, bacterial infections, haemoglobinopathies.

- Nutritional anaemia: intolerance to peppery foods, angular stomatits, glossitis, atrophy of buccal mucosa and tongue pappilae.

Severe anaemia (Hb<7g/dl, Hct 0.20):SYMPTOMS:

• Headache

• lethargy,

• Faintness

• Palpitations

• Breathlessness at rest

• Indigestion

• Giddiness

• Swelling of legs.

Severe anaemia (Hb<7g/dl, Hct 0.20):SIGNS:

• Pallor: skin, tongue, oral mucosa, palms, nail beds become more marked.

• High Pulse/heart rate.

• Visible vigorous neck pulsations

• Soft systolic murmurs – dilated heart chambers

• Wide pulse pressure

• Lower limb soft oedema.

• Proteinuria from renal hypoxia may occur.

• Weight loss.

Very severe anaemia (Hb <4g/dl Hct:0.14)

• Above symptoms worsen

• Signs of hyperdynamic circulation worsen

• Cardiac failure

• Hypovolaemia

• Pancytopaenia may result from severe folate deficiency, due to thrombocytopaenia, a pt may present with ecchymosis and petechial haemorrhage.

Cardiac failure

•Occurs due to myocardial oxygen lack.

Signs:

- orthopnoea

- engorgement of neck veins

- presence of rales at lung bases.

•Mortality >50% if unattended.

Hypovolaemia

• In very severe anaemia plasma volume increase in response to the drop in red cell volume, however not enough to make up for the reduction in red cell volume = fall in total blood volume as much as 40% of normal.

• Possible adv. Increase in Hb conc. At the expense of even less blood loss during preg. delivery.

• In such situation a blood loss as little as 200mls can cause death.

COMPLICATIONS Maternal:

• Repeated infections due to decreased body resistance to infections.

• Preterm labour,

• late abortions.

• Cardiac failure

• Circulatory shock

• Lack of normal extravolume reserve.

• Puerperal sepsis

• Impaired involution of uterus.

• Lactation difficulties.

Fetal:•Prematurity

•IUGR

•IUFD

•Birth asphyxia

•Immature immunity

•Less Fe and folate stores.

INVESTIGATIONS

• RBC count, Hb, Hct level

• Stained blood film, evidence of Fe, Folate def.

• Hb electrophoresis

• Urine microscopy and culture

• Blood grouping

• Stool microscopy

• CXR

• HIV test

• Cancer markers

• Abd USS: abd preg.

• Serum Fe conc.( n= 125mg/dl)

• Fe binding capacity (n= 400mg/dl)

• Transferrin saturation (n= 30%)

MANAGEMENT •An appropriate antenatal care, health education and

prophylactic use of haematinics, important preventive measures.

• Treatment should be continued for at least 2 months to build up body stores of Fe and in endemic areas to protect the mother from malaria.

• Important: specific targeting.

MGT FE DEF. ANAEMIA•Diet: Liver, meat, kidney, eggs, green vegetables.

•Oral ferrous sulphate tab 200mg twice daily in comb. With FA 5mg daily treatment of choice.

• Side effects: nausea, vomiting, heartburn, constipation, abdominal cramps, diarrhoea.

•Vit A supplementation in areas known with Vit A def. Rec. dose: retinol 2.4mg (5000IU)

Parenteral Fe:

• Indications:

- Malabsorption syndrome

- Intolerance to oral Fe

- Need to rapid response

• Preparations:

- Iron dextran complex: IV or IM.

- Iron sorbitol citrate complex: IM only

• Side effects:

- IM is irritant, painful, stains skin, less absorbed

- IV better in small repeated dose but may be ass. With flushing, urticaria, arthralgia, fever, lymphadenopathy, phlebitis, and anaphylaxis.

• Dose: instructions usually given with the products. Calculations made from actual Hb, desired Hb, Body wt.

Antihelmintics:

•Albendazole 400mg single dose.

•Mebendazole 200mg twice daily for 3 to 5 days.

•Mebendazole 500mg stat.

Megaloblastic anaemia

•FA treatment of choice, rarely Vit B12.

•FA tabs 5mg daily, well tolerated and response is usually favourable.

•Proven Vit B12 def. Parenteral Hydroxocobalamin 1mg 6 doses over 2 to 3 wksfollowed by I every 3 months.

Malaria chemoprophylaxis

•In P.falciparum endemic areas malaria chemoprophylaxis has been found to improve preg outcome.

•Intermittent presumptive treatment with SP 3 tabs at 20 – 24 and 30 – 32wks is done in Tz.

Blood transfusionGiven when:

• Incipient or established heart failure with Hct = or < 0.14 (4.0g/dl). 40mg lasix, 50mg ethacrynic acid given 10 min before a transfusion is started which has to run for 6hrs, preferably PCV.

• Anaemia of less severity coexists with serious disease e.g. Sepsis, renal failure, haemorrhage, haemoglobinopathy or eclampsia.

• Severely anaemic women who are seen for the first time during labour/aborting

• Those with anaemia and major surgery is unavoidable.

• Choice of the blood product depends on severity of anaemia and clinical circumstances.

• Oxygen given when required by mask.

Anaemia in labour• Risk of death in anemic pts increase during labour and 12 hours

postpartum.

• Precipitate labour is common esp. in multiparous women because fetal size is small.

• Excess blood loss, surgery and anesthesia are all poorly tolerated because of underlying hypoxia.

• In severe/very severe anemia Iv fluids during labour are dangerous.

• Emphasis: correct blood loss.

• Intermittent oxygen may be required and is given by mask.

• Careful attention to asepsis and use of prophylactic antibiotics.

•Episiotomy best avoided. If done + tears prompt repair should be done.

•Active mgt of 3rd stage of labour to minimize blood loss.

•Avoid use of ergometrine: use Oxytocin/Misoprostol