O&G Update August 2013

Primary Horizontal version

Dr Cindy Pang Consultant Dept of Obstetrics & Gynaecology

Heavy Menstrual Bleeding (HMB)

Management of

In a normal menstrual cycle, the average woman loses a total of 30-40 ml of blood over three to seven days. Heavy or prolonged menstrual bleeding is termed menorrhagia. Research criteria define this as a monthly menstrual blood loss in excess of 80 ml. A more practical definition may be that of menstrual loss that is greater than the woman feels she can reasonably manage. When the term menorrhagia is used, it is implied that there is regular, cyclical bleeding without inter-menstrual bleeding. The National Institute for Health and Clinical Excellence (NICE) in the UK defines heavy menstrual loss as excessive blood loss that interferes with a woman’s physical, social, emotional and/or quality of life.

Causes of heavy menstrual bleeding include: 1. Dysfunctional uterine bleeding (excessive bleeding with no identifiable pathology): 20-40% 2. Anovulatory cycles (more common at extremes of reproductive age): 20%.

3. Local causes: fibroids, endometrial polyps, adenomyosis, endometritis, pelvic inflammatory disease 4. Endometrial hyperplasia and carcinoma: to consider in patients with non-cyclical heavy bleeding who are above 40 years old or with risk factors such as polycystic ovarian syndrome, obesity, nulliparity, early menarche, diabetes mellitus, unopposed exogenous or endogenous estrogen.

5. Systemic disease: including hypothyroidism, liver or kidney failure and bleeding disorders.

History and Examination

Treatment

Studies have shown that there is little correlation between the number of pads or tampons used and actual menstrual blood loss. This is because hygiene habits of women differ greatly. However, it is prudent to enquire in the history about the extent of use and staining of sanitary products, as well as occurrences of clots or flooding, as a gauge of the amount of loss. Other pertinent information from history-taking includes:

Pregnancy, endometrial hyperplasia and endometrial carcinoma need to be ruled out. If there are organic causes of menorrhagia, such as fibroids or adenomyosis, treatment options can be offered based on the patient’s wishes and fertility concerns.

1. The pattern of bleeding and associated symptoms - inter-menstrual bleeding, post-coital bleeding, dyspareunia and pelvic pain.

2. Fertility wishes 3. Symptoms of anaemia 4. Effect on quality of life, including any time off work 5. Past medical problems, including clotting disorders, thyroid status and gynaecological history 6. PAP smear, gynaecology history Clinical examination should be undertaken to assess for any anaemia and also to rule out potential organic causes of HMB. bio-prosthetic aortic valve is preferred because no anticoagulation is required.

Investigations Always consider a urine pregnancy test to rule out pregnancy. PAP smear should be undertaken if not done recently.

Ultrasound (ideally transvaginal) is the first-line diagnostic tool for identifying structural abnormalities such as fibroids and polyps. An endometrial thickness of less than 12 mm is normal in premenopausal women.

Endometrial sampling should be offered to women above 40 years, particularly if there is non-cyclical (irregular) bleeding. Menorrhagia (regular, heavy bleeding) is generally not associated with malignancy though endometrial evaluation is usually performed in older women.

Younger women who have not responded to medical treatment for heavy menstrual bleeding should also be offered endometrial evaluation.

A full blood picture will give an estimation of the degree of anaemia.

Other blood tests such as thyroid function tests and bleeding disorder testing should be performed only if there is clinical suspicion.

The general considerations guiding the choice of initial treatment are: • • • • •

Etiology and severity of bleeding Associated symptoms (eg. pelvic pain, infertility) Fertility - Contraceptive needs or plans for future pregnancy Contraindications to hormonal or other medications Patient preferences regarding medical versus surgical and shortterm versus long-term therapies

In the absence of any structural or histological abnormalities, or fibroids more than 3cm causing distortion of uterine cavity, the recommendations for treatment according to the NICE clinical guideline 44 on heavy menstrual bleeding (January 2007) are: First line: 1. Levonorgestrel intrauterine system - Mirena • This is long-term treatment and can last for five years. Studies have shown this to be more effective than other medical treatments.

• This option reduces blood loss by up to 94%. Some women experience an increase in irregular or heavy bleeding during the first three months after placement of the LNG-IUS. After six months, the majority of patients have amenorrhoea or oligomenorrhoea Second line: 1. Tranexamic acid • This is an anti-fibrinolytic agent. It inhibits the dissolution of clots which then reduces menstrual flow. It can reduce flow by up to 50% and is usually taken on the 3 heaviest days of the period 2.

Non-steroidal anti-inflammatory drugs (NSAIDs) such as mefenamic acid

3. Combined oral contraceptive pill (COC) • There is suppression of gonadotrophins and reduction of menstrual blood loss by around 40%.

• Other benefits include improvement of dysmenorrhoea, more regulation of the menstrual cycle, improvement in pre-menstrual symptoms, reduction of the risk of pelvic inflammatory disease and protection of the ovaries and endometrium against cancer.

MICA (P) 101/05/2013 A Quarterly May - Aug 2013

Surgical options The choice of treatment will depend on both the uterine size and the patient’s desire to retain her uterus.

1. Endometrial ablation • This option can be considered if the uterus size is less than 10 weeks gestation on palpation.

• This involves removing the full thickness of the endometrium together with the superficial myometrium.

2. Hysterectomy

Vertical Version

Different Variations

• This option can be considered when other options have been exhausted and the patient chooses not to retain her fertility. It is 100% effective but carries surgical risks.

The available treatment options are summarized in the following table.

Method

Reduction in Menstrual loss

Levonorgestrel IUS (Mirena)

94%

Irregular bleeding

Contraception, can treat endometriosis

Tranexamic acid

50%

Insignificant

Nil

Mefenamic acid

30%

Gastritis

Analgesia for dysmenorrhoea

Combined oral contraceptive

40%

Risk of thrombosis, breast cancer risk in longer term

Reduces dysmenorrhoea, contraception

Endometrial ablation

>90%

May require repeat treatment

Nil

Hysterectomy

100%

Surgical risks, infertility

Eliminates subsequent risk of uterine/cervical cancer

Side effects

Other benefits

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Obstetrics and Gynaecology Head A/Prof Tan Hak Koon Senior Consultant Prof Charles Ng Prof Ho Tew Hong Dr Yu Su Ling Prof Tay Sun Kuie Dr Yong Tze Tein Dr Chua Hong Liang Dr Tan Lay Kok Dr Devendra K (Chief Editor, OGN) Dr Tan Wei Ching Dr Chew Ghee Kheng Dr Peter Barton-Smith Consultant Dr Hemashree Rajesh Dr Tan Eng Loy Dr Cindy Pang Associate Consultant Dr Jason Lim Registrar Dr Ravichandran N Dr Renuka Devi Dr Serene Lim Liqing Dr Helen Barton-Smith

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Iron Deficiency (ID) and Iron Deficiency Anemia (IDA) in Infants

Anaemia in pregnancy – a common problem Management of

Heavy Menstrual Bleeding (HMB)

Services Antenatal Counselling for High Risk Pregnancy Neonatal Intensive Care Neonatal High-Dependency and Normal Nursery Neonatal Screening Child health Screening Ambulatory Paediiatrics Universal Hearing Screening Developmental Screening

• The reduction in blood loss is by 30% and is usually taken on the 3 heaviest days of the period. Side-effects include nausea, vomiting and diarrhoea.

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Appointment: 6321 4377 Centre for Assisted Reproduction (CARE): 6321 4292 Early Pregnancy Unit (EPU) Hotline: 6321 4516 Prenatal Diagnostic Centre (PDC): 6321 4516 http://www.sgh.com.sg

Dr Vijay Baral Consultant Dept of Neonatal & Developmental Medicine

Iron Deficiency (ID) and Iron Deficiency Anemia (IDA) in Infants

Pathogenesis

Although exclusive breastfeeding is sufficient to maintain iron stores for the first 6 months of life, iron-containing complementary foods will be required to maintain reserves after this period. Iron-fortified cereals along with foods containing meat should be introduced from 6 months. Foods rich in Vitamin C are encouraged to increase dietary absorption and bioavailability of non-haem iron in the diet. Cow’s milk can be introduced from 12 months to meet calcium needs of the infant (600ml) but larger volumes may be associated with ID due to the displacement of iron-rich foods from the diet.

Iron deficiency (ID) is the commonest nutrient deficiency in children and is often accompanied by iron deficiency anaemia (IDA). UNICEF estimates that 40-50% of children in developing countries aged less than 5 years old may have ID. Iron is essential for synthesis of haemoglobin and a substrate for various enzymatic processes. It is important for myelination, neurotransmitter function and brain development. Iron is absorbed in the small intestine, with haem iron (present in meats) being better absorbed than non-haem iron (found in vegetables). Iron is extensively recycled from ageing red blood cells. Vitamin C promotes absorption whereas phytates (in cereals and pulses) and tannins (in tea) inhibit absorption. Iron is absorbed onto transferrin and stored as haemosiderin and ferritin (1 ng/ml = 8mg Iron). Table 1 lists iron requirements in infancy.

A nutrient-rich balanced diet should be encouraged after this time in healthy toddlers but those at risk of poor dietary iron may need a prolonged use of iron-fortified milk. Infants and toddlers should avoid drinking tea because tannins in tea inhibit iron absorption.

Treatment of Iron Deficiency Anemia (IDA)

Table 1: Iron requirements in infancy and early childhood

Treatment of choice for IDA is ferrous sulphate 3 - 6mg/kg/day given as a single or twice daily dose for a minimum of 3 months. Ferrous fumarate has equivalent bioavailability but is less palatable.

Preterm infants: 2-4mg/kg/day when given orally Term infants (Birth - 6months): 0.27mg/day Term infants (7 - 12 months): 11mg/day Toddlers (1 - 3 years): 7mg/day

Treatment should be stopped once haematological parameters have normalised. Compliance is sometimes poor due to taste preferences, constipation and treatment duration. Iron supplements may be combined with fruit juice rather than milk to increase bioavailability and palatability.

Source: Institute of Medicine, Washington, DC; 2003

No

Insignificant

Nil No

• Treatment is oral ferrous sulphate 3 – 6 mg/kg/day for 3 months or until improvement in haematological parameters.

Serum iron

Low

<12 μmol/l

Total iron binding capacity

Low

<15%

Folate deficiency: Test

MCV

Hb (g/L)

SF (ng/ml)

MCV

4

105

20

73

103

39

76

6

105

9

71

111

19

68

9

100

5

71

114

14

70

110

Low (the first test of the full blood count indices to indicate iron deficiency) but can be normal Low

• Preterm and at-risk infants must receive 3 mg/kg/day of oral elemental Iron from 4 weeks of life till 12 months of life.

SF (ng/ml)

10

73

Specific treatment level

MCHC

FORMULA-FED INFANT

73

Finding in iron deficiency

• Diagnosis is based on haematological parameters (Hb, MCV, serum ferritin) • Exclusively breastfed full term infants have sufficient iron stores for the first 6 months of life after which dietary supplementation with ironrich food is recommended.

Hb (g/L)

10

MCV

• Poor maternal diet, prematurity, intra-uterine growth restriction and infant malnutrition are common causes of iron-deficiency anemia.

Table 2: Normal levels of haemoglobin (Hb), serum ferritin (SF), Mean corpuscular volume (MCV)

110

It is useful to investigate anaemia with a haemoglobin electrophoresis. However, in severe iron deficiency, thalassaemia trait may be indistinguishable from iron deficiency anaemia. An electrophoresis will diagnose thalassaemia and sickle cell traits. In Singapore, thalassaemia major in the fetus is excluded by looking for a MCV ≥ 80 FL in either partner in their full blood counts (FBC). This is because a MCV of ≥ 80 effectively excludes thalassaemia as a cause of the anaemia. If both partners have a MCV less than 80 FL, haemoglobin electrophoresis should be done for both to exclude thalassaemia trait. Women and their partners who are found to have low MCVs can also be referred to the National Thalassaemia Registry where specific testing for thalassaemia can be performed at subsidised rates (call 63941863).

Test

• Iron deficiency is the commonest nutritional deficiency worldwide and is associated with developmental delay and poor neurological function in pre-school children.

Iron deficiency is accompanied by changes in laboratory parameters, with Haemoglobin (Hb) and Mean Corpuscular Volume (MCV) reflecting anaemia while serum Transferrin saturation (TS) and Ferritin (SF) reflect iron stores. Ferritin is an acute phase reactant and may be raised if there is coexisting infection or inflammation. Table 2 shows the normal values of Hb, SF and MCV.

12

Ideally screening at booking and again at 28 weeks should be carried out during a woman’s antenatal care. A high proportion but not all women will require iron supplements. An electrophoresis should also be offered to all women at booking and if there is evidence of a haemoglobinopathy then the partner should also be tested and appropriate counselling offered.

SUMMARY

Diagnosis of Iron deficiency

Age (months)

Investigations

Iron deficiency anaemia:

Iron Deficiency (ID) may be caused by inadequate intake or absorption. Maternal health during pregnancy is an important determinant of iron status in the foetus. Majority of iron stores are laid down in the last trimester of pregnancy. Hence, preterm infants are at greatest risk of ID as a consequence of preterm birth. This is often aggravated following birth when the preterm infant experiences significant blood loss from frequent sampling, rapid postnatal growth and low availability of dietary iron. In older children, iron deficiency may result from blood loss secondary to hookworm infestation or chronic bowel enteropathy with IDA being the sequelae of ID.

BREASTFED INFANT

The commonest cause for anaemia in pregnancy is iron deficiency and this article will focus on this and the treatment. The next commonest cause is folate deficiency, which is commoner in women taking anticonvulsants or folate antagonists e.g. sulfasalazine. Folate deficiency is also commoner in sickle-cell disease, thalassaemia, and hereditary spherocytosis. Haemoglobinopathies are more uncommon but they should be screened for.

Anaemia in pregnancy – a common problem

Background

Dr Helen Barton-Smith Registrar Dept of Obstetrics & Gynaecology

Finding in folate deficiency

Indication to start treatment

MCV

Raised

No

Serum folate

Low

No

Red cell folate

Low

No

Treatment All women should be given at least 400mcg of folic acid daily, ideally from 3 months preconceptually until 12 weeks, to minimize the risk of neural tube defects. However the standard preparation dose in Singapore is 5mg. This higher dose is recommended for women who have neural tube defects or a history of a pregnancy affected with a neural tube defect, diabetics or are taking anticonvulsants.

Prevention of iron deficiency

The World Health Organisation (WHO) found the global prevalence of anaemia in pregnancy women was 41.8%. Studies have shown an association with serious consequences in pregnancy. Iron deficiency anaemia is associated with low birth weight, preterm delivery and an increase in the blood loss at delivery.

The recommended dietary intake of iron in women of child bearing age is 27 mg/day. Mothers must be screened during pregnancy to ensure that they take a well-balanced diet rich in the essential nutrients, especially iron, calcium, and folate. Mothers who are iron-deficient will require adequate supplementation. Iron-rich foods include not only fish and meat but also non-haem sources such as green leafy vegetables, kidney beans, lentils, sunflower seeds, soybeans, tofu and raisins.

Physiologically there is an increase in the plasma volume during pregnancy, mostly by 34 weeks, and this causes a dilutional effect lowering the haemoglobin (Hb) concentration, haematocrit and red cell count. However it does not affect the mean corpuscular volume (MCV) or the mean corpuscular haemoglobin concentration (MCHC). During pregnancy the lower limit of haemoglobin concentration is taken to be 11g/dl. The woman’s iron requirements increase in pregnancy, due to increasing red cell mass and fetal demands.

In the newborn period, strategies like delayed clamping of the umbilical cord, reducing blood sampling, top-up transfusions as clinically indicated, promoting breast feeding and supplementing iron in preterm babies may reduce the incidence of iron deficiency anaemia in infancy.

Women who have heavy menses or have had a previous pregnancy recently, or known to be previously anaemic have a much higher chance of developing anaemia or worsening anaemia in their pregnancy.

For those who cannot tolerate the treatments parenteral iron is an option. However the evidence is conflicting if the rate of increase in haemoglobin concentration is faster compared to oral therapy. This is much safer now than previously. Parenteral iron used to have an associated risk of anaphylaxis, but newer preparations have a much lower risk. It does, however, require IV administration. Women with thalassaemia minor should be given folic acid and iron supplements throughout pregnancy but parenteral iron should not be given.

Clinical features

In severe cases, or those who become progressively more anaemic despite treatment, they may require a blood transfusion. But the significant risk of blood transfusions in women of child bearing age is not infection, commonly believed by the public, but the risk of developing atypical antibodies which may cross the placenta in a future pregnancy and cause fetal anaemia and serious complications for a future baby.

Iron in breast milk is very well absorbed and will be sufficient to meet the needs of a normal-weight, full term exclusively breast-fed infant for 6 months. Non-breastfed newborns should receive iron-fortified infant formula after birth.

In the breastfed preterm infant born at less than 32 weeks or weighing < 1800g, iron supplementation is recommended from 1 month of life. Iron may also be recommended in babies who are born small for gestational age (defined as birth weight less than 10th centile for gestational age), growthrestricted or having malabsorption syndromes (often post-surgery). Infants must receive 3mg/kg/day of elemental iron (0.5ml/kg/day of ferrous sulphate) till 12 months old. An alternative to ferrous sulphate / ferrous fumarate is Iron (III)-hydroxide polymaltose complex (1-2 drops/kg).

Do note that 1ml (20 drops) of the polymaltose complex contains 50mg elemental iron.

Often anaemia is detected on antenatal screening tests but testing can be prompted by clinical symptoms of lethargy, dizziness or fainting.

However, these are often common symptoms associated with normal pregnancy. It very rarely results in cardiovascular signs.

Nearly all women will need iron supplementation to prevent iron deficiency in pregnancy. All women should have multivitamin supplementation and these preparations contain adequate iron for the majority of women. Luckily iron is better absorbed from the gut during pregnancy but this can be further improved by drinking supplements with ascorbic acid (vitamin C), and avoiding tannins in chocolate, coffee and tea.

Treatment of those who are already anaemic should be recognised and started as early as possible. Taking daily iron will raise the Hb by about 0.8-1g/dl per week so starting later in the third trimester is less effective.