INTRODUCTION

Pregnancy anaemia is defined by hae­moglobin (Hb) of less than 110g/l in the first or third trimester or less than 105g/l in the second trimester. Iron deficiency with or without anaemia has many ad­verse effects on the nervous system, in­tellectual capacity, physical performance, immune response and pregnancy out­come(Fairbanks & Beutler1995, Baynes1994). The mother may be overwhelmed by easy fatigability, dyspnoea, headache, reduced exercise tolerance and weak­ness. On the other hand, the fetus may encounter an increased risk of low birth weight and preterm delivery.

Up to 30% of women in the post-partum period are affected by anaemia of under 10g/dL and about 10% by severe anae­mia of less than 8%. By far the main cause for this is the deficiency of iron supplied during pregnancy and blood loss during and after birth(Lebrecht et al. 1995).Under normal circumstances, oral iron is the treatment of choice since it is simple, effective, safe and cheap. How­ever, oral iron is better absorbed in an empty stomach but patient may experi­ence side effects such as nausea, vom­iting, gastritis, diarrhea and constipation. These side effects can be minimized by co-administration with food, although this may substantially decrease absorption, particularly of ferrous preparation(Perewusnyk et al. 2002). Even a patient who responds well to oral iron therapy would require a long time, usually months to reach the target haemoglobin level. This means that they have to suffer from iron deficiency for extended periodsun­necessarily(Al-Momen et al. 1996).

A pregnant woman without anaemia may require at least 1000mg of elemental iron to be delivered to the haemopoietic organs while the anaemic patient may need more than 2600mg. This require­ment cannot be met by the oral route in the majority of patients because of limited absorption, bio-availability and compli­ance(Bynumet al. 1977, Lee & Feldman1993, Kahrilas & Hogan1993).

Parenteral iron therapy with intravenous iron-sucrose complex (Venofer) was first introduced to UKMMC in 2002.  It has been used to correct anaemia in preg­nant women in whom the elemental iron requirement cannot be met by oral route. Previous studies have shown that intra­venous Venofer is safe and effective in pregnant and post-partum women with iron deficiency anaemia(Breymann et al. 2000, Al-Momen et al. 1996).

OBJECTIVE

The aim of this study was to assess if administration of intravenous iron su­crose complex (Venofer) was a sensible option in treating iron deficiency anaemia in pregnancy and puerperium using day­care clinic in an urban hospital. A favor­able outcome would imply its safe usage as an outpatient for treating anaemia in pregnancy. 

METHODOLOGY

This was a cross-sectional observational study, recruiting all patients with iron de­ficiency anaemia who were referred to the Obstetrics Day Care Unit, UKMMC for intravenous Venofer. The study was completed in 18 months from March 2003 to August 2004. Baseline haemo­globin (Hb) level was determined and reassessed in 14 daysafter treatment. Patients’ demography, number of visits to the Day Care Unit, total dosage, incre­ment of haemoglobin level, adverse ef­fect and their compliance to complete the full therapy were recorded. Patients with other causes of anaemia such as thalas­semia trait, haemolytic anaemia, liver or renal disease were excluded.

Calculation of Venofer dosage

For body weight of above 35 kg, the tar­get Hb is 120 g/l and depot iron is 500mg.  

*Factor = 0.0034 x 0.07 x 1000

(iron content of Hb ~0.34%; Blood vol­ume ~7% of body weight; factor 1000 is conversion from g to mg)

Administration of Venofer

The first 25mg of iron (i.e. 25mls of solu­tion) was infused as a test dose over a period of 15 minutes. If there were no adverse events the remaining portion of the infusion was given. Infusion of 200mg iron sucrose in 200ml normal saline over 1 hour 30 minutes was administered at an interval of 1 to 3 days to complete the total dose required.

RESULTS

A total of 120 patients were recruited. There were 70% Malay, 16% Chinese, 10% Indian and 4% from other ethnic background. About half the patients (48%) were working mothers, 45% were housewives and 7% were students.

The mean gestational age of those who were referred for anaemia in pregnancy was at 34.5 weeks. The pre-treatment Hb level was 8.5+0.85g/dl (7.2-8.9g/dl). In the post-partum group, the pre-treatment Hb was 7.6+0.80g/dl (7.2-8.8g/dl). Major­ity of these patients (92%) had a history of either non-compliance or intolerable to oral iron supplement, hence were offered intravenous Venofer. The other 8% re­quired rapid restoration due to recent blood lost from post-partum haemor­rhage.

Of those who completed treatment, the mean increment of Hb within 14 days was 3.52g/dl (2.9-4.6g/dl). Each patient received an average of seven ampoulesi.e. 700mg of Venofer. 

Majority of the patients tolerated the treatment well with no discomfort or any significant complaint (Table 1). One pa­tient developed skin rashes while on in­fusion. She responded to intravenous Chlorpheniramine Maleate (Piriton) and the Venofer was completed at a slower infusion rate. Another patient had low-grade pyrexia of 38^oC after receiving her second dose and the fever settled with Paracetamol. Seven patients complained of having a mild metallic taste and 15 patients had nausea. There were no other undesirable effects such as head­ache, dizziness, palpitations, dyspnoea, vomiting, abdominal pain, diarrhoea, muscle cramps, myalgia, shivering, chest pain, injection site pain, anaphylactic re­action or hospitalization for further treat­ment.

Of the 120 patients who were recruited for the study, 10 patients (8.3%) did not complete their therapy - eight of them were antenatal mothers who delivered before completion of treatment; another two post-partum patients defaulted their follow-up.

Venofer was approved as a formulary item and patients received free supply be it as an in or outpatient. However, the ward charge for an in-patient in UKMMC was RM45 per day. As most patients re­quired at least a three-day infusion, it was estimated that each patient might save up to RM135. Our estimation was that during the study period on the 120 outpatients, a total of RM 16,200 hospi­talization fee was avoided.

DISCUSSION

Anaemia is a common deficit in preg­nancy. Though traditionally it is treated by oral haematinics, some may require parenteral iron due to poor compliance to oral supplement, poor absorption or in­tolerable gastro-intestinal side effects. Prior to year 2002, intra-muscular prepa­ration iron dextran (Imferon) was the available parenteral preparation in UKMMC  However, iron dextran is to be discouraged because of its adverse ef­fects including pain at injection site, ir­regular absorption, staining of buttock and rarely, malignancy(Martini et al. 1994, Roberson1973).       

Parenteral iron using iron-sucrose com­plex (Venofer)has largely replaced iron dextran. Numerous reports from Euro­pean countries have proven its effective­ness and patient tolerability (Al-Momen et al. 1996, Perewusnyk et al. 2002). The results of ourobservational study have shown that iron-sucrose complex is safe, is well tolerated and effective in treating anaemic pregnant and postpartum pa­tients in a day care setting. There were 120 patients in this study, twenty-four sustained minor adverse effects such asskin rash,low-grade pyrexia,metallic tasteand nausea.There was no serious side effects or anaphylactic reactions reported.

Iron-sucrose complex releases ironto the iron-binding proteins with a half-life of about 6 hours. This relatively short half-lifegrants iteffectiveand carries minimal risk of allergic reaction(Danielson1998, Kraftet al. 2000, Rohlinget al. 2000). Skinrash and fever can be prevented by giving a slow infusion over one to four hoursordividing the total dose into smaller portions(100-200mg/day).Theside effects are mostly self-limited and resolve with symptomatic treatment.

Unlike other parenteral iron prepara­tions, iron-sucrose complex istaken up mainly by the reticuloendothelialsystem and notby the parenchymal cells of the liver, kidney, adrenal gland or other or­gans.Therefore, organic toxicity such as pancreatic, myorcardial or hepatic he­mosiderosis is less likely even with iron-sucrose complex over-load (Macdougall et al. 1989).

Majority of the patients (92.8%) in this study completed the treatment course. The local urban population around UKMMC has proven themselves to be highly compliant to outpatient treatment, regardless of their background as housewives, working mothers or stu­dents. Outpatient treatment allows less interruption to family or working life, is more convenient and cost saving. The avoidance of hospitalization could itself encourage patients’ compliance.

Although iron-sucrose complex is ex­pensive and the treatment requires intra­venous infusion and is time consumingas compared to oral iron supplement, it is highly tolerated and rapidly effective.This study showed thatthe mean increment of Hb within 14 days was 3.52g/dl (2.9-4.6g/dl). On the contrary, oral iron takes a longer time to achieve the target hae­moglobin level and the increment rate is significantly slower (Al-Momen et al. 1996). It is very important to correct an anaemic pregnant patient before delivery, as the maternal iron status will influence the newborn iron status as well. Infants of anaemic mothers are more likely to be­come anaemic at 12 months of age, even when possible confounders such as socio-economic status, feeding practices and morbidity were taken into account(Colomer et al.1990). In conclusion, out­patient treatment of anaemia in preg­nancy and post-partum period using Venofer is safe, feasible, with high pa­tient compliance and saves cost from hospitalization fees.