Bleeding may occur from a maternal, fetal or placental site (Table 12.2). Both placental and maternal sites involve loss of maternal blood, whereas in the case of vasa praevia fetal blood is lost.

Table 12.2 Causes of antepartum haemorrhage

Maternal	Placental	Fetal
Vaginal infectionstart=”row” colname=”col1″ align=”left”(e.g. Candida, Trichomonas)	Placenta praevia	Vasa praevia
Cervical ectropion	Placental abruption
Cervical infection
Cervical malignancy
Bloody show
Uterine rupture

In many cases the cause of bleeding cannot be identified. It is likely that these small bleeds represent minor abruptions and such women should be carefully monitored as they are at risk of further abruption. If repeated bleeds occur, then fetal growth restriction also may develop. The term ‘marginal bleed’ is sometimes used to refer to such bleeding.

Non-vaginal causes of bleeding also may occur. Bleeding from haemorrhoids is common in pregnancy, for example, and haematuria may also be mistaken for vaginal blood loss.

History

Important features in the history of a woman presenting with suspected APH are:

• The colour, consistency and amount of blood loss. Placenta praevia blood loss tends to be fresh and red whereas blood associated with abruption may be darker. It is useful to attempt to quantify loss by comparing it to the patient’s usual menstrual loss or number of pads used.

• The duration of bleeding and any possible triggering factors, such as sexual intercourse.

• Any previous bleeding episodes.

• Abdominal pain – a feeling of uterine ‘tightening’ or pelvic discomfort are all important features suggesting a possible placental abruption. Bleeding associated with a placenta praevia tends to be painless (80%), unless labour has started.

• Labour – a small amount of blood loss is common with a ‘show’ and more significant bleeding may occur during precipitate labour. A mucus-like blood loss, rupture of membranes or contractions may, therefore, suggest APH due to labour.

• Fetal movements – bleeding with loss of fetal movements is suspicious of abruption.

• The date and result of the most recent cervical smear and details of any previous sexually transmitted or other genital infections, such as candida.

• Placental site, as described in the most recent ultrasound report.

• The Rhesus status of the woman.

Examination

Owing to the increased circulating volume of pregnancy, a woman may lose more than 500 ml of blood before her vital signs are affected. Even where little blood loss is noted vaginally, in cases of placental abruption there may be significant ‘concealed’ loss within the uterus, resulting in hypovolaemia. Therefore, other indicators of shock should be noted carefully, such as pallor, peripheral vasoconstriction (’cold and clammy’), dizziness or a general feeling of being unwell. Overt signs such as tachycardia, hypotension and a reduced level of consciousness imply life-threatening haemorrhage has occurred.

Abruption is also often associated with pre-eclampsia and hypertension or proteinuria may, therefore, be present.

Abdominal palpation may elicit tenderness, uterine tightenings (spontaneous uterine contractions that may not be felt by the mother) or uterine irritability (uterine contractions in response to palpation of the uterus). Placental abruption may be associated with either high-frequency contractions or with a hard uterus (‘woody’) due to tonic contraction.

A high fetal head or malpresentation, with a soft uterus, is suggestive of placenta praevia (obstructing the descent of the presenting part into the pelvis).

Speculum examination in women with APH should never be performed until placenta praevia has been excluded by ultrasound scan. Where the placenta is known to be low, speculum examination should usually be avoided as it will be unlikely to add further information and may risk precipitating further bleeding.

If the placenta is not low, speculum examination should be performed and the colour, consistency and volume of any blood or of liquor or other discharge seen should be noted. Bleeding may be seen to come from the endocervical canal or it may be possible to identify the cervix or vagina as the source of bleeding.

The cervix itself should be inspected for dilatation, ectropion, polyps and signs of infection or possible malignant lesions.

Any lesions of the vulva or anus should also be noted if they might be possible alternative sources of blood loss.

Investigations

Women reporting APH should all have the following investigations:

• FBC

• Blood group

• Serum save

• Crossmatch – depending on the estimated blood loss

• Coagulation studies – if a coagulopathy is suspected or blood loss is massive. Low fibrinogen, increased D-dimer, prolonged prothrombin time and APTT, and low platelets suggest DIC, usually following abruption

• Kleihauer test – particularly important for Rhesus-negative women to determine the dose of anti-D required. The result of a Kleihauer test is not immediate enough, however, to help in initial management.

• CTG – commenced as early as possible to ascertain fetal well-being and monitor uterine activity.

• Ultrasound – requested urgently if the placental site is unclear, to look for placenta praevia. Retroplacental blood clot may be visualized on scan after an abruption, but it is often not, and if a large clot is present then the likelihood is that fetal demise has already occurred and the woman is extremely unwell. Abruption is, therefore, essentially a clinical diagnosis, though ultrasound may help to exclude placenta praevia as an alternative cause of the bleeding.

• High vaginal swab – to exclude Candida and full vaginal and cervical swabs should be sent if an infective cause of bleeding is suspected.

Management

All women reporting APH should be admitted to hospital. Further management is determined by the severity of the maternal haemorrhage, the fetal condition and gestational age. (The only exception to routine admission may be where bleeding is confirmed to be due to a non-obstetric cause and has ceased, such as a single postcoital bleed associated with an obvious visible cervical ectropion, in a woman with a high placenta and no other risks for placental abruption.)

If estimated blood loss is slight, intravenous access should be obtained and the woman may be observed and discharged 24 hours after the last fresh (red) loss. Rhesus-negative women should be given anti-D.

Women with significant bleeds should have two large-bore intravenous cannulae inserted and aggressive fluid resuscitation and transfusion if necessary. Other blood products, such as platelets and fresh frozen plasma, should be given where indicated. Intensive monitoring and continuous CTG are indicated. Specific management thereafter depends on the cause of the loss.

Both placenta praevia and placental abruption are associated with a high risk of postpartum haemorrhage, and active management of the puerperium with Syntocinon and ergometrine at delivery followed by a Syntocinon infusion is necessary. The management of postpartum haemorrhage is covered in Chapter 17.

Placenta praevia

Placenta praevia is implantation of the placenta in the lower segment of the uterus, occurring in 1% of pregnancies at term. It is classified according to how close the leading edge of the placenta is to the internal cervical os, as shown in Figure 17.1. Bleeding may occur due to the thinning of the cervix and lower segment of the uterus in late pregnancy or in early labour. If bleeding occurs in a woman with placenta praevia, then admission until delivery is normally necessary. The mother should have regular haemoglobin measurement and anaemia treated with iron or blood transfusion, if necessary. Four units of crossmatched blood should be readily available in case of sudden haemorrhage.

The fetus is generally not affected by bleeding from a placenta praevia unless maternal hypovolaemia occurs, but regular CTG is advisable. Delivery by caesarean section at term should be performed unless bleeding is uncontrolled or labour occurs, in which case premature delivery may be necessary. Delivery should be carried out by a senior obstetrician and senior anaesthetist with blood for transfusion immediately available.

In some cases a low placenta may still move from the internal os near term and the clinical finding of a deeply engaged head and accurate determination of the placental site by transvaginal ultrasound may confirm this.

In rare cases where the placenta is suspected to be clear of the os, but some doubt exists, examination under epidural in theatre may confirm the presence of the head and no palpable placenta in the pelvis, and artificial rupture of membranes (ARM) can be carried out. Theatre staff should be ready for immediate caesarean section if bleeding occurs.

Placental abruption (abruptio placentae)

Placental abruption is the premature separation of a part of the placenta from the uterus, before delivery of the baby. Bleeding occurs from the placental bed and a haematoma develops beneath the placenta, shearing it from the uterus. Bleeding may be seen vaginally, or it may be concealed entirely inside the uterus. As a result, the amount of visible or external bleeding may not necessarily correlate with maternal blood loss or grade of abruption.

The fetus is at risk from an abruption due to hypoxia from the sudden reduction in placental gas exchange function. Intrauterine death is, therefore, common.

Abruption is the commonest identifiable cause of intrauterine death and occurs in approximately 0.5–1% of pregnancies, but the reported incidence depends on the diagnostic criteria used. Risk factors for abruption are hypertension, pre-eclampsia, previous abruption (10% recurrence), multiple pregnancy, diabetes, tobacco or cocaine use and trauma (e.g. road traffic accident or assault to the abdomen).

A mild abruption may present with a small amount of pain or bleeding that settles spontaneously with no apparent effect on fetal well-being. Major abruption usually presents with constant lower abdominal or back pain and varying amounts of vaginal blood loss, depending on the degree to which the blood is concealed behind the placenta. A small amount of visible blood loss associated with a woman who is in pain, pale, clammy, tachycardic or hypotensive is classical, and should be treated as a life-threatening emergency.

Management of a suspected abruption includes admission to the labour ward, insertion of two large-bore intravenous cannulae, crossmatching of 4 units of blood and correction of any coagulopathy. If the estimated blood loss is significant, the urinary output should be monitored via a urinary catheter and a central venous line may be inserted to manage fluid balance more accurately. The management of obstetric haemorrhage is covered further in Chapter 17. Continuous CTG is commenced if the fetus is still alive.

Minor abruption, with minimal estimated blood loss and no apparent maternal or fetal compromise, may be managed expectantly, with observation and regular monitoring of CTG, fetal movements and fetal growth by ultrasound.

More commonly, delivery will be indicated. Vaginal delivery in the context of abruption is associated with less blood loss and less risk to the mother than caesarean section. Commonly, abruption stimulates spontaneous labour and delivery is quick. Alternatively, prostaglandin or ARM may be used to induce the labour.

Emergency caesarean section may be indicated if the CTG suggests fetal compromise or the blood loss is uncontrollable. At caesarean, couvelaire uterus may be found, where blood has penetrated the myometrium, resulting in a purplish bruised appearance and inability for the uterus to contract.

In view of the risk of clotting deficiency, epidural or spinal anaesthesia is avoided until clotting studies have been performed.

If pre-eclampsia is present, this must be treated simultaneously.

The dose of anti-D for a Rhesus-negative woman who has had an abruption depends on the size of the fetomaternal haemorrhage. This may be determined by the Kleihauer test.

Complications of placental abruption

The most serious complication to the mother is DIC, with low clotting factors, fibrinogen, platelets and renal failure. This should be anticipated and treated aggressively. Postpartum haemorrhage is also common due to the coagulopathy and to the often poorly contractile uterus.

Table 12.3 summarizes the differences between the typical presentations of placenta praevia and placental abruption, but it should be remembered that many presentations are atypical and that the two conditions may coexist.

Table 12.3 Summary of the differences between placenta praevia and placental abruption

Placenta praevia	Placental abruption
Painless (80%)	Constant pain or high-frequency contractions
Clinical condition correlates	Clinical condition suggests more
with visible blood loss	blood loss than visualized
Soft, non-tender uterus	Tender, tense uterus
High presenting part or	May be unable to palpate fetal parts
malpresentation	due to tense uterus
Ultrasound diagnosis	Clinical diagnosis
Low risk to the fetus	Fetus at high risk
Caesarean section essential	Caesarean only if bleeding
	uncontrolled or fetal compromise

Uterine rupture

Uterine rupture is an extremely rare cause of vaginal bleeding, usually occurring in labour in a woman with a history of previous uterine surgery such as caesarean section or myomectomy. The predominant feature is pain (though this may be partially masked by an epidural), with sudden cessation of contractions and CTG abnormalities. Haematuria and maternal tachycardia are other clinical signs. Immediate laparotomy should be performed to deliver the baby and control maternal haemorrhage.

Vasa praevia

‘Vasa praevia’ is the term used where umbilical cord vessels abnormally traverse the membranes and overlie the internal cervical os. It occurs in 1 in 3000 pregnancies and is associated with either a velamentous insertion of the cord into the placenta (from the side) or with a succenturiate (satellite or accessory) lobe of placenta (Fig. 12.2). The vessels are at risk of tearing when they are stretched during cervical dilatation in labour or during ARM.

Figure 12.2 Illustration of a normal placenta showing (A) central cord insertion, (B) a velamentous (lateral) cord insertion and (C) a placenta with a succenturiate lobe. B and C both predispose to vasa praevia.

Fetal mortality from vasa praevia is 35–95% as the fetus exsanguinates unless the condition is quickly diagnosed, immediate caesarean section performed and the neonate transfused.

There is no significant risk to the mother from vasa praevia.

Diagnostic tests for fetal blood from the vagina are available, but are not in general clinical practice and the diagnosis must, therefore, be suspected clinically by a combination of relatively small-volume blood loss (less than 500 ml), no maternal pain and an abnormal CTG, often following ARM.

Occasionally, vasa praevia may be diagnosed antenatally on ultrasound with demonstration of Doppler flow in the vessels beneath the fetus, in which case elective caesarean section should be arranged.

Cervical lesions

Various cervical lesions may account for APH. The commonest is a cervical ectropion, which may be diagnosed on speculum and managed conservatively. Cauterization is avoided in pregnancy and the ectropion often resolves in the puerperium. Infections such as Trichomonas may cause cervicitis and bleeding and should be treated accordingly (see Chapter 9).

Cervical polyps are occasionally found in pregnancy and again should be managed expectantly, with consideration of avulsion only if bleeding is uncontrolled, and with great care paid to haemostasis due to the increased cervical vascularity in pregnancy.

Cervical cancer is rarely suspected or diagnosed in pregnancy. Biopsy should generally be reserved for cases where suspicion is very high, because of the risk of heavy bleeding. If cervical cancer is confirmed, then multidisciplinary team management should determine the optimum time and method of delivery.

Infections of pregnancy

Urinary tract infection

Asymptomatic bacteriuria, UTI and pyelonephritis are discussed under the maternal systemic disorders section, below.

Chickenpox

Chickenpox, caused by the varicella-zoster virus, occurs in up to 3 in 1000 pregnancies. Spread is by respiratory droplets and incubation is 14–21 days.

Maternal infection

The typical itchy vesicles appear over the trunk, face and limbs following prodromal malaise and fever. The vesicles burst, with scabs developing over the next few days. Sufferers are infectious from 48 hours before the rash until the last vesicles have crusted over. Ninety per cent of women are immune because of childhood infection and this can be confirmed on the booking blood sample.

If infected, pregnant women develop more severe complications, with a 10% risk of pneumonia and up to 1% mortality. Other complications are encephalitis, hepatitis and DIC.

Diagnosis is usually clinical, but if there is doubt an increase in immunoglobulin (IgG) G can be detected over a 2-week period. Non-immune women with definite exposure to chickenpox may benefit from varicella-zoster immunoglobulin given in the first 10 days after exposure to prevent clinical disease.

Women should be seen in the community, avoiding exposure to other pregnant women, with admission for antiviral and supportive therapy if pneumonia is suspected.

Risk to the fetus

Two per cent of fetuses develop fetal varicella syndrome (dermatomal skin scarring, eye defects, limb hypoplasia and neurological defects) if infection occurs prior to 16 weeks. Occasional cases have occurred up to 20 weeks. Urgent assessment in the fetal medicine department should be arranged for ultrasound signs of fetal infection.

Chickenpox developing from 48 hours before to 5 days after delivery carries a > 25% chance of varicella infection of the newborn, though it may rarely occur with infection any time in the last 4 weeks of pregnancy. The condition is fatal in 30%. If delivery cannot be delayed until more than 5 days after the onset of the rash, then the baby should be treated with intravenous aciclovir and varicella-zoster immunoglobulin.

Rubella

Rubella (German measles) is very rare, as a result of widespread immunization of teenagers and now infants. Spread is by person-to-person contact and the incubation period is 14–21 days.

Maternal infection

The typical clinical features involve a flu-like illness with associated fine macular rash, particularly over the trunk, though 20–50% of infections are asymptomatic. The disease lasts a few days and no specific maternal management is required. Women are infectious from 1 week before to 1 week after the onset of the rash.

Susceptibility varies with vaccination trends and immigration, but approximately 2% of nulliparous women are susceptible. Infection is thought to occur in 2/1000 of these susceptible (absent or low-level antibody) women.

Diagnosis is confirmed by serological testing for antibody levels.

Risk to the fetus

If the mother develops rubella in the first trimester, there is an 80% chance of the baby becoming infected, compared with a 25% chance at the end of the second trimester. One hundred per cent of infected babies have the characteristic rubella abnormalities, which include cataracts, congenital heart disease, sensorineural deafness, learning difficulties, hepatosplenomegaly and microcephaly. The teratogenic effects are worst for infections at earlier gestations.

Many parents opt for termination of pregnancy if infection occurs, especially in the first trimester.

Adult rubella and congenital rubella syndrome are notifiable diseases.

Toxoplasmosis

Toxoplasma gondii is a parasite and maternal infection may occur by ingestion of cysts or oocytes from raw, cured or poorly cooked meat, unwashed fruit and vegetables, unpasteurized goats’ milk, or food contaminated by soil or cat faeces. Lambing is also a risk factor for infection.

Maternal infection

The incidence of toxoplasmosis in pregnancy is about 2 in 1000, in whom about 40% fetal infection occurs (15% in the first trimester and 70% in the third trimester). Thirty per cent of pregnant women in the UK are immune due to previous infection. Incubation is 5–23 days. Clinical features are uncommon, but can include flu-type symptoms and lymphadenopathy, with a rare prolonged glandular fever-type illness.

Diagnosis by serial serological testing in the mother is complex, as seroconversion does not indicate timing of infection, which may have been up to 12 months earlier.

Treatment of the mother with spiramycin may reduce the chance of fetal infection.

Risk to the fetus

Transplacental Toxoplasma infection may occur 4–8 weeks after maternal infection and the effects include miscarriage, stillbirth, growth restriction, hydrocephalus, deafness and blindness. Although fetal infection is more likely at later gestations (15, 25 and 65% affected in first, second and third trimesters, respectively), the effect on the fetus is worse at earlier gestations. Amniocentesis or cordocentesis may be used to diagnose fetal infection. Babies infected in the third trimester often appear normal at birth, with blindness developing during childhood.

Prevention of toxoplasmosis involves washing all raw food and vegetables before cooking, ensuring meat is thoroughly cooked before eating, not reheating cooked meals, wearing gloves to garden and avoiding cat litter.

Salmonella

Salmonella is a Gram-negative bacterium that may be contracted by ingestion of contaminated raw or partially cooked eggs, raw meat and chicken. The incubation period is 12–72 hours and gastroenteritis occurs with severe vomiting, dehydration and fever. The infection appears to be more common in pregnancy, but there is no direct effect on the fetus.

Cytomegalovirus

Cytomegalovirus (CMV) infection affects at least 3 in 1000 of all live births. CMV is the leading infective cause of congenital neurological impairment in children.

The virus is transmitted through urine, saliva and other body products.

Maternal infection

CMV has a 3–12-week incubation period and the illness is usually asymptomatic (90%) but may cause a flu-like illness. The virus often continues to be shed after infection. One per cent of women develop either primary or reactivated CMV infection in pregnancy.

Maternal immunity can be detected by IgG in the blood and primary infection can be confirmed with IgM.

Risk to the fetus

If primary infection occurs in pregnancy, then there is a 10–15% risk to the fetus. If the mother is already seropositive and continuing to shed following infection then the risk to the fetus is only 1%.

Fetal infection may occur at any gestation and be diagnosed by identification of the virus on amniocentesis or cordocentesis samples. From 10 to 20% of infected babies may have evidence of infection at birth (e.g. hydrops, IUGR, microcephaly, hydrocephalus, hepatosplenomegaly and thrombocytopenia), but 80–90% develop symptoms later such as mental handicap, visual impairment, progressive hearing loss or psychomotor retardation.

Screening for CMV in pregnancy is not indicated as there is no treatment, women with positive serology can have reactivated disease and it is not possible to predict which babies will be affected and how seriously.

Listeria

Listeria monocytogenes, a Gram-positive coccus, is found in unpasteurized dairy products such as soft cheese and in pâté, soil and animal faeces. Lambing is a specific risk factor for infection.

The incidence in pregnancy is higher than in the normal population (12 versus 0.7 cases per 100 000 women) and the illness may be more severe with fever, headache, malaise, backache, abdominal pain, pharyngitis or conjunctivitis. Severe respiratory complications and meningitis can also occur. The incubation period varies from 3 to 70 days. Diagnosis is made by identification of the organism in blood culture, placenta or neonatal swab culture and treatment is with high-dose penicillin.

Infection in the fetus can result in miscarriage, stillbirth, preterm delivery and neonatal listeriosis (50% mortality).

Parvovirus

Parvovirus B19 infection occurs in fewer than 1% of adults in the UK each year. Transmission occurs via respiratory droplets and the incubation period is about 18 days. Infectiousness occurs from 5 to 15 days after infection. Outbreaks of infection tend to occur in schools (erythema infectiosum, fifth disease, slapped-cheek syndrome). Infection in adults may involve fever, malaise and arthralgia, and is asymptomatic in 20%. Immunity is confirmed by detection of IgG in the serum. Diagnosis of infection is made on serial IgM measurements, 3 weeks apart.

Risk to the fetus

Transplacental infection occurs in up to 30% of pregnant women with parvovirus, with fetal death in 9%. The risk is highest when infection occurs in the second trimester. The commonest finding is non-immune hydrops (from a chronic haemolytic anaemia and myocarditis).

Fetal monitoring with ultrasound to detect hydrops should be performed for up to 12 weeks after maternal infection. Intrauterine transfusion or early delivery may be needed.

Pregnant women exposed to parvovirus, such as staff at a school during an epidemic, should probably be advised to take time off for a few weeks, especially in the second trimester.

HIV

Human immunodeficiency virus (HIV) infection is discussed in Chapter 9. The incidence of HIV infection is up to 1 in 200 pregnant women in some areas of the UK. Transmission occurs by sexual contact (heterosexual or homosexual), infected blood products (e.g. needle sharing) or vertical transmission.

In pregnancy, many women are now diagnosed as a result of inclusion of HIV testing in routine antenatal screening programmes. Some women, however, will be known to be infected prior to pregnancy.

Pregnancy does not have an adverse effect on HIV disease or viral load. The pregnancy may be affected, however, by HIV infection if the mother is very underweight or has another HIV-associated illness.

Infection of the baby may occur by transplacental spread, by infected blood at delivery (through mucous membranes at the mouth, nose, conjunctivae) or through breast milk.

Neonatal HIV infection is more likely in the presence of:

• High viral load

• Low CD4 lymphocyte count

• Preterm labour

• Prolonged rupture of membranes (> 4 hours)

• Invasive procedures (fetal blood sampling, instrumental delivery, episiotomy, fetal scalp electrode).

Antenatal management

Management in pregnancy involves careful counselling and support. Antiviral therapy is usually started and viral load, CD4 count and platelet count are monitored.

Confidentiality is paramount, as many women will not have told their partners, friends and family about the infection.

Management around delivery

The following four strategies combined reduce the chance of neonatal HIV infection from about 25% to less than 5%:

1. Caesarean section delivery, ideally maintaining intact membranes until the head has been delivered and avoiding contact between the baby and the maternal blood

2. Delivery within 4 hours if spontaneous rupture of membranes occurs, ideally by caesarean section

3. Zidovudine prophylaxis intravenously to the mother for 4 hours prior to delivery and to the baby orally for 6 weeks postnatally

4. Avoidance of breastfeeding.

The baby can be tested for infection by polymerase chain reaction techniques in the neonatal period, or by antibody test, once the maternal antibody has cleared from the baby’s circulation (about 3 months).

Group B streptococcus

Group B streptococcus (GBS) (Streptococcus agalactiae) colonization of the vagina occurs in approximately 25% of women at some stage in their pregnancy. It is generally asymptomatic in the mother, but is responsible for early-onset neonatal sepsis in 1 in 2000 births. This disease is fatal in 6% of term infants and 18% of preterm infants, accounting for approximately 1 in 65 of all neonatal deaths.

The risk factors for neonatal group B streptococcus infection are shown in Table 12.4. Women with any of these risk factors should be treated with intrapartum high-dose intravenous penicillin (3 grams stat followed by 1.5 grams every 4 hours) or 8-hourly clindamycin 900 mg (if penicillin-allergic).

Table 12.4 The maternal risk factors for neonatal group B streptococcus (GBS) infection and indications for antibiotic prophylaxis

Previous GBS-affected baby

Colonization with GBS at any time in the current pregnancy

GBS bacteriuria in the current pregnancy

Preterm labour (< 37 weeks)

Prolonged rupture of membranes

Pyrexia in labour

Neonatal death has not been shown to be reduced by either routine screening in pregnancy with lower vaginal and rectal swabs or antenatal treatment of colonized women.

Bacterial vaginosis

Bacterial vaginosis is present in 12% of pregnant women in the UK and is asymptomatic in at least 50%. Symptoms are a fishy odour and creamy discharge. Presence of bacterial vaginosis in early pregnancy almost doubles the risk of preterm delivery and late miscarriage. However, although antibiotics such as metronidazole eradicate the infection effectively, they do not reduce the perinatal risks. Therefore, treatment is only indicated for symptomatic women.

Sexually transmitted infections and Candida in pregnancy are discussed further in Chapter 9.

Maternal systemic disorders

Maternal systemic disorders are a common reason for referral of women to the obstetrician-led antenatal clinic. Multidisciplinary team management is important for many such conditions, in particular diabetes, thyroid disease, cardiac, renal and haematological disorders.

Haematological disorders

Anaemia

Anaemia is the commonest medical disorder of pregnancy.

Aetiology

Anaemia may be pregnancy-related, in which case iron deficiency is the commonest cause. Other causes are folate deficiency (e.g. poor diet, thalassaemia), chronic disease (e.g. renal disease), pre-existing anaemia (e.g. from menorrhagia, recent pregnancy) and haemoglobinopathy.

Pathophysiology

In pregnancy, iron absorption increases in response to the increased maternal, placental and fetal demands. The subsequent increase in red cell mass is about 20%. However, plasma volume expands by 40–50% and the haemoglobin concentration therefore falls. This is exacerbated if dietary iron is insufficient. The normal lower limit for haemoglobin concentration at booking is 11 g/dl and drops to 10.5 g/dl after 28 weeks.

Clinical features

Breathlessness, palpitations, tiredness and dizziness are the common symptoms of anaemia, though some women are asymptomatic.

Pallor, pale nails and pale conjunctivae as well as tachycardia may be noted on examination.

Low haemoglobin is associated with low birth weight and preterm labour as well as increased risk of transfusion for the mother if haemorrhage occurs at delivery.

Investigations

Routine FBC at booking and at 28 weeks may detect anaemia. Otherwise, FBC should be checked when anaemia is suspected clinically.

Iron deficiency is diagnosed with a low mean cell volume (MCV), mean cell haemoglobin and mean cell haemoglobin concentration. It may be confirmed if necessary by a low serum iron, total iron-binding capacity and low serum ferritin.

Folate deficiency presents with a raised mean cell volume and may be confirmed by a low serum and red cell folate concentration.

Pregnant women may have a mixed folate and iron-deficiency picture.

Haemoglobinopathy screen should be checked if not done at booking.

Treatment

Many types of iron therapy are available and the ferrous compounds are better absorbed than the ferric compounds. The usual preparation is ferrous sulphate 200 mg three times a day. Liquid preparations, such as ferrous fumarate, may be prescribed for women intolerant of tablets. Side effects of oral iron include nausea, epigastric discomfort and constipation.

A course of injectable iron is used rarely for women intolerant of any oral preparations, but does not increase iron concentration any faster than oral preparations. The expected increase in haemoglobin from oral or injectable iron is 2 grams in 3–4 weeks.

Transfusion is rarely used for anaemia in pregnancy.

Folic acid 5 mg daily should be given for folate deficiency, women taking anticonvulsants and those with haemoglobinopathies. There is no evidence for routine iron or folic acid supplementation for prophylaxis in pregnancy except for women with multiple pregnancies.

Venous thromboembolism

Incidence

VTE remains the leading cause of maternal death. The incidence in non-pregnant women is 5 in 100 000 per year and in pregnant women is 60 in 100 000 per year. VTE occurs at all gestations and is also common postnatally.

Risk factors

Risk factors for VTE are shown in Table 12.5.

Table 12.5 Risk factors for venous thromboembolism in pregnancy and the puerperium

Pre-existing risk factors:
Previous venous thromboembolism
Age over 35 years
Smoking
Obesity (body mass index > 30 kg/m² at booking)
Parity > 4
Gross varicose veins
Paraplegia
Congenital thrombophilia
antithrombin deficiency
protein C deficiency
protein S deficiency
factor V Leiden
Acquired thrombophilia
antiphospholipid syndrome
Thrombocythaemia
Polycythaemia
Sickle-cell disease
Inflammatory disorders, e.g. inflammatory bowel disease
Other systemic disease, e.g. nephrotic syndrome, cardiac disease
Risk factors developing during pregnancy:
Hyperemesis
Dehydration
Ovarian hyperstimulation syndrome
Long-haul travel
Severe infection, e.g. pyelonephritis
Immobility (> 4 days’ bed rest antenatally, intrapartum or postnatally)
Surgical procedure in pregnancy or puerperium, e.g. caesarean section, evacuation of retained products of conception, postpartum sterilization
Pre-eclampsia
Excessive blood loss
Prolonged labour
Midcavity instrumental delivery
Immobility after delivery

Pathophysiology

Virchow’s triad describes the pathophysiological factors contributing to thrombus development:

1. Increased blood viscosity (e.g. increased clotting factors in pregnancy, thrombocythaemia, antiphospholipid syndrome (APS))

2. Decreased blood flow (impeded circulation in lower limbs from gravid uterus, reduced mobility)

3. Endothelial damage (e.g. pelvic vein trauma at delivery).

Clinical features

Clinical features are often non-specific and have a poor predictive value in the diagnosis of VTE. VTE may present at any stage in the pregnancy or puerperium.

History

Women may report a swollen and red calf, usually on the left. Symptoms may be vague or acute and severe. Deep-vein thrombosis (DVT) in the ileal or femoral vein may present with a swollen leg, which may be painful and white in extreme cases (phlegmasia alba dolens).

Pulmonary embolism characteristically causes breathlessness, pleuritic chest pain, cough or haemoptysis. Collapse or sudden death may occur with a large pulmonary embolism. Many small emboli are asymptomatic.

Examination

General examination may reveal a low-grade pyrexia, or tachycardia. A swollen tender red calf or leg may be seen. Iliofemoral DVT is common in pregnancy and may be asymptomatic or show the classical white swollen leg.

A large pulmonary embolism may be associated with hypotension, tachypnoea, raised jugular venous pressure, loud second heart sound or right ventricular heave. Reduced air entry and a pleural rub may also be heard.

Investigations

D-dimer

D-dimer, a fibrin degradation product, is usually raised in pregnancy, but the test has good negative predictive value if normal.

Imaging

Duplex ultrasonography can be used to image the veins, looking for DVT in the lower limb. However, thrombosis below the knee or above the inguinal ligament may be difficult to visualize and ultrasound imaging for DVT is operator-dependent. Further imaging, for example with magnetic resonance venography, should be requested if there is clinical suspicion. Contrast venography, with abdominal shielding, is occasionally still used to diagnose DVT where ultrasound is not available.

Investigations where pulmonary embolism is suspected include electrocardiogram (sinus tachycardia, right axis deviation, right bundle branch block or occasionally the classical ‘S1Q3T3’), oxygen saturation, arterial blood gas and chest X-ray (hypoperfusion, infarction, effusion). Spiral computed tomography (CT) or V/Q scan causes minimal radiation to the fetus and may be needed to confirm the diagnosis. Angiography and magnetic resonance imaging are alternative investigations.

Treatment

Women should be treated on clinical suspicion of VTE until the diagnosis has been confirmed or refuted. The commonest treatment now is a therapeutic dose of low-molecular-weight heparin (LMWH), calculated according to maternal weight. This is safe and effective in pregnancy, but intravenous unfractionated heparin is an alternative, with monitoring of APTT.

Graduated elastic compression stockings should be worn and the affected leg should be elevated initially, with mobilization after a few days.

Pulmonary embolism should be managed in liaison with the physicians. Treatment is essentially anticoagulation and supportive measures such as oxygen and monitoring of pulse, blood pressure, oxygen saturation and electrocardiogram.

Thrombolysis or embolectomy should be considered where a thrombus is large or the symptoms do not improve on anticoagulation treatment.

Long-term heparin in pregnancy is associated with some loss of bone mass, but osteoporosis is rare. The platelet count may also drop and women should have platelets checked at 3 days and after 1 month of treatment.

The rest of the pregnancy should be managed in liaison with a haematologist, with a decision made whether to commence warfarin or continue heparin. The woman should remain on prophylactic anticoagulation until at least 6 weeks after delivery. Warfarin, though usually avoided in pregnancy, is safe in the puerperium and with breastfeeding.

VTE prophylaxis during pregnancy, delivery and postpartum

Women with a past history of VTE should be offered LMWH prophylaxis for 6 weeks postpartum. If there is a persisting risk factor, history of recurrent VTE, a positive family history or the thrombophilia screen is positive, then LMWH should also be prescribed antenatally.

All women should be encouraged to mobilize early after delivery and keep well hydrated.

Additional measures such as thromboembolic stockings and prophylactic heparin should be considered after delivery for women with other significant risk factors. Generally, all women with three or more existing risk factors from Table 12.5 should be given LMWH prophylaxis for 3–5 days following delivery. However, age over 35 and obesity are particularly significant risks and prophylaxis should be considered for women who have both risk factors.

Postpartum LMWH should be given as early as possible, though if an epidural or spinal anaesthetic has been given, it should be delayed until 4 hours after the spinal or insertion or removal of the epidural catheter.

Pneumatic boots are another method of reducing VTE risk associated with caesarean section.

Antiphospholipid syndrome

APS, an acquired thrombophilia, causes arterial and venous thrombosis, recurrent miscarriage, and increased risk of pre-eclampsia, fetal growth restriction and placental abruption. Antiphospholipid antibodies (anticardiolipin antibody and lupus anticoagulant) are found in 2% of the general population, but it is unclear what proportion of these women has the syndrome. APS may be primary, or secondary to lupus disease.

Diagnosis of APS depends on:

• Three first-trimester miscarriages

• One midtrimester miscarriage

• Severe pre-eclampsia, IUGR or abruption, necessitating delivery prior to 37 weeks

and the presence (on two samples, at least 6 weeks apart) of:

• Anticardiolipin antibodies

• Lupus anticoagulant.

Treatment

The management of APS depends on the presenting features. Recurrent miscarriage and pregnancy complications such as pre-eclampsia, growth restriction and abruption are discussed in the relevant sections of this book.

In subsequent pregnancies, women with APS and a previous poor obstetric history should be given aspirin prophylaxis (75 mg daily), which is safe and effective at prolonging pregnancy and improving outcome. Daily prophylactic dose LMWH is also indicated in some women to reduce the chance of VTE, IUGR and pre-eclampsia.

All women with APS should have regular blood pressure and fetal growth monitoring.

Women with APS are also at increased risk of thrombosis during and after pregnancy and a low threshold for thromboprophylaxis should be used for prolonged immobilization or operative delivery. Women with previous thrombosis need thromboprophylaxis throughout pregnancy and the puerperium.

A multidisciplinary approach with a haematologist is recommended.

Thrombocytopenia

Up to 10% of women have a low platelet count in pregnancy, most commonly due to gestational thrombocytopenia. The causes of thrombocytopenia are shown in Table 12.6.

Table 12.6 Causes of thrombocytopenia in pregnancy

Common causes:
Gestational thrombocytopenia
Autoimmune idiopathic thrombocytopenia
Uncommon causes:
Thrombotic thrombocytopenic purpura
Antiphospholipid syndrome
Human immunodeficiency virus (HIV)-related
Drug-induced thrombocytopenia
Pre-eclampsia
Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome
Disseminated intravascular coagulation

Clinical features

Most women are found to have an incidental low platelet count on routine antenatal testing, or in labour. Haemorrhage or easy bruising occurs when the platelet count is less than 50 × 10⁹/l.

Investigation

Initial low platelet results should be repeated to exclude clumping of platelets as a cause. It may also be necessary to confirm the low platelet count on a blood film or citrate sample. Where the cause of thrombocytopenia is not immediately clear, platelet autoantibodies and HIV status should be checked and blood pressure and urinalysis should be checked to exclude pre-eclampsia.

Gestational thrombocytopenia

The platelet count decreases for most women throughout pregnancy. If it falls below 150 × 10⁹/l, it is termed gestational thrombocytopenia.

Once diagnosed, the platelet count should be monitored every 2 weeks antenatally and checked again in labour. It is rare for the platelets to fall below 100 × 10⁹/l. Epidural is usually contraindicated with platelets less than 80 × 10⁹/l.

There is no effect on the baby.

Autoimmune idiopathic thrombocytopenia

Autoimmune idiopathic thrombocytopenia is caused by antiplatelet antibodies resulting in maternal platelet destruction and thrombocytopenia. It is not pregnancy-specific, but is commonly diagnosed in and exacerbated by pregnancy. Diagnosis is normally made after exclusion of other causes, or by detection of the antibodies.

Management involves monitoring the platelet count every 2 weeks. High-dose corticosteroids are indicated when the platelet count falls below 50 × 10⁹/l. Intravenous gammaglobulin can also be used to increase the platelet count rapidly, with an effect lasting for about 2 weeks.

Platelet transfusions are only rarely given for autoimmune thrombocytopenia, for example if regional anaesthesia or operative delivery is anticipated, with no opportunity for IgG or steroids to work.

The fetus is affected in approximately 5% of cases of idiopathic thrombocytopenia where IgG antibodies cross the placenta and cause neonatal thrombocytopenia. The clinical features include neonatal or antepartum cerebral haemorrhage. Babies of affected mothers should therefore have regular platelet checks for the first 4 days.

Alloimmune thrombocytopenia

Alloimmune thrombocytopenia is fetal thrombocytopenia as a result of maternal antiplatelet antibodies directed against fetal platelets. The maternal platelet count is normal.

It occurs in 1 in 2000 births and is usually diagnosed after a first affected pregnancy where the baby shows signs of thrombocytopenia and haemorrhage. Thereafter, all pregnancies are at high risk and are managed in a fetal medicine department with serial fetal platelet counts (by cordocentesis) and intrauterine platelet transfusions as necessary. Instrumental deliveries, fetal blood sampling and fetal scalp electrode are all contraindicated at delivery and caesarean section is usually considered to minimize risk of haemorrhage for the baby.

Endocrine disorders

Insulin-dependent diabetes mellitus

Incidence

Insulin-dependent diabetes mellitus (IDDM) affects 4 in 1000 pregnant women.

Pregnancy is a state of insulin resistance and glucose intolerance, due to the anti-insulin effects of human placental lactogen, cortisol and glucagon from the placenta. Insulin requirements in diabetic women, therefore, increase in pregnancy.

The fetus in a diabetic pregnancy becomes hyperinsulinaemic because of the high maternal glucose level. Neonatal hypoglycaemia then occurs due to the sudden loss of maternal glucose.

Diabetes is associated with a variety of pregnancy complications, as listed below, but good glycaemic control prior to and during pregnancy reduces these, and all diabetics must be strongly advised to see their diabetic team before becoming pregnant, for comprehensive counselling. For the fetus, the risks of maternal IDDM are miscarriage, fetal abnormality (5–25%), IUGR, macrosomia, polyhydramnios, sudden intrauterine death and increased neonatal mortality. Specific congenital abnormalities include cardiac disease, neural tube defects and sacral agenesis. For the mother, pre-eclampsia (especially if she has pre-existing hypertension or nephropathy), infections and difficult glycaemic control with more hypoglycaemic attacks, as well as increasing insulin requirements, are likely. Diabetic nephropathy and renal disease are likely to worsen, and should preferably be screened for and treated before pregnancy.

The risks of maternal IDDM are summarized in Table 12.7.

Table 12.7 The risks of diabetic pregnancies

Maternal risks:

Difficult glycaemic control and increased hypoglycaemic episodes

Occasional diabetic ketoacidosis (e.g. with undercurrent infection, hyperemesis, steroids or tocolytics)

Worsening of diabetic retinopathy

Worsening of diabetic nephropathy

Increased risk of pre-eclampsia (especially with pre-existing hypertension or nephropathy)

Increased risk of infections

Fetal risks:

Congenital abnormality (5–25%)

Miscarriage

Infection (Candida, urinary tract infection, wound infection, endometritis)

Preterm delivery (20% risk)

Intrauterine growth restriction

Macrosomia

Polyhydramnios

Shoulder dystocia

Cord prolapse

Sudden intrauterine death

Neonatal risks:

Neonatal hypoglycaemia

Neonatal respiratory distress syndrome

Jaundice

Polycythaemia

Increased neonatal mortality

Clinical features

Insulin requirements usually double during pregnancy and the increase is most marked as the fetus grows most rapidly between 28 and 32 weeks. Hypoglycaemic episodes are also more common in pregnancy and women may be less aware of these in pregnancy. However, hypoglycaemia does not affect the fetus as long as the mother is given appropriate oral carbohydrate or glucagon.

Management

Prepregnancy

Prepregnancy consultation, as discussed in Chapter 11, is crucial for diabetic women as tight glycaemic control prior to pregnancy reduces the risk of fetal congenital abnormality and miscarriage. The number of insulin injections may be increased and a different combination of short- and longer-acting insulins used to maintain the blood glucose between 4 and 5 mmol/l. Non-insulin-dependent diabetics are usually converted from oral hypoglycaemic agents to insulin.

Antenatal

Hyperemesis may need to be managed as an inpatient if the blood glucose control is poor. Antenatal management should then be based in a specialist antenatal diabetic clinic, with visits generally every 2 weeks initially and then weekly from 34 weeks.

A detailed scan is needed in the first and second trimesters in view of the increased risk of fetal abnormality and a fetal cardiac scan should also be arranged for the second trimester. Serum screening for Down’s syndrome must be used with an appropriate reference group as oestriol, βhCG and alpha-fetoprotein are all reduced in diabetic women. Nuchal translucency may, therefore, be a better screening test in diabetic women.

Retinopathy should be screened for, as there is a risk of significant deterioration in pregnancy. Nephropathy should be assessed initially with urinalysis testing for proteinuria and if present, with a 24-hour urinary protein collection and urea, creatinine and electrolytes.

Blood glucose measurements should be recorded before and after meals at least 3 days per week, with confirmation of these results with glycosylated haemoglobin and random glucose measurements in clinic. Ideal measurements are < 5.0 mmol/l fasting and < 7.5 mmol/l postprandial. To achieve this, most women have their insulin regime altered in pregnancy, if not prepregnancy, to improve glucose control, for example with a greater number of injections (three short-acting and one intermediate/long-acting at night). Polyhydramnios occurs when maternal glucose levels are high.

Ultrasound scans are arranged every 4 weeks until 32 weeks, then every 2 weeks to detect macrosomia and polyhydramnios.

If steroids are to be administered, or tocolytics such as ritodrine are indicated, insulin-dependent women need admission for intravenous sliding-scale insulin.

In labour

The risk of sudden stillbirth in babies of diabetic mothers is the indication for early delivery. Most diabetic women should be delivered between 38 and 39 weeks.

The mode of delivery depends on previous obstetric history, estimated fetal weight and predicted risk of shoulder dystocia. Overall, 60% of diabetic women are delivered by caesarean section.

A sliding scale of insulin and dextrose should be commenced in labour (or prior to caesarean section) as stress and abnormal eating patterns in labour disrupt the mother’s normal insulin regime and also because good predelivery maternal glucose control reduces the chance and severity of neonatal hypoglycaemia.

The baby should have early regular blood glucose measurement and feeds.

Postnatal

The insulin dose is reduced immediately after delivery to the prepregnancy regime, as insulin requirements return to the non-pregnant state within 24 hours. In practice this is done when the woman first eats after delivery. In breastfeeding women, the insulin should be reduced to only two-thirds of the normal dose due to the risk of hypoglycaemia.

All diabetics should have a 6-week endocrinological review.

Gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance of varying severity with onset or first recognition during pregnancy. The incidence is up to 3%, depending on the diagnostic criteria used and the ethnic background of the relevant pregnant women.

Diagnostic criteria

The diagnostic criteria for GDM are controversial, but the most commonly quoted are World Health Organization definitions after a 75-gram glucose load:

• 2-hour venous glucose < 7.8 mmol/l: normal

• 2-hour venous glucose 7.8–11 mmol/l: impaired glucose tolerance

• 2-hour venous glucose > 11 mmol/l: gestational diabetes.

These definitions may overdiagnose GDM because they are based on a non-pregnant population and there is a slowed glucose response in normal pregnancy.

A glucose tolerance test for all pregnant women is not recommended, but screening tests are recommended for women with higher risk factors:

• Glycosuria

• Macrosomia or polyhydramnios

• Previous GDM

• Previous macrosomic baby or stillbirth

• Body mass index greater than 30

• Strong family history of diabetes.

As glucose tolerance worsens with advancing gestation, GDM is best diagnosed in the second trimester.

Clinical features

Most women have no clinical features, but are diagnosed after screening because of high-risk features as outlined above. GDM is associated with an increased risk of macrosomia and pre-eclampsia, but not of congenital abnormality.

Management

Initial management is dietary, involving reduced fat and carbohydrate and increased fibre in the diet. Postprandial blood glucose level above 7.5 mmol/l or fasting blood glucose above 5.5 mmol/l is an indication for insulin in addition to diet restriction.

Ultrasound scan at 28, 32 and 36 weeks will detect macrosomia and polyhydramnios, which help the decision regarding timing and mode of delivery.

Screening for pre-eclampsia involves vigilant monitoring of blood pressure and urinalysis. Postnatally, women should have a glucose tolerance test at 6 weeks to exclude diabetes.

The rate of hyperthyroidism in pregnancy is 0.2%. Ninety-five per cent of these have Graves’ disease, in which increased circulating T₄ levels are the result of TSH receptor-stimulating antibodies. Hyperthyroidism may improve or deteriorate in pregnancy.

Clinical features

Most women are on antithyroid treatment prior to pregnancy, but features of thyrotoxicosis may be present if the dose is insufficient or the diagnosis has not been made. Symptoms include heat intolerance, weight loss, insomnia, palpitations and vomiting and clinical signs are tachycardia, lid lag and exopthalmos.

Investigations

In untreated hyperthyroidism TSH is low and free T₃ and T₄ are raised.

Management

Carbimazole and propylthiouracil both cross the placenta, but are relatively safe in normal doses, though carbimazole can occasionally cause scalp defects in the fetus. Beta-blockers may rarely be needed for severe thyrotoxicosis in pregnancy. Radioiodine is contraindicated in pregnancy and for 4 months before conception because of the risk of fetal thyroid destruction.

Women with hyperthyroidism should be seen monthly and T₄ maintained at the high end of the normal range.

Effect on the baby

Babies may be hypothyroid due to transplacental passage of antithyroid drugs, or hyperthyroid due to passage of thyroid-stimulating antibodies, especially if the thyrotoxicosis is of recent onset or poorly controlled. At delivery the baby should have thyroid function checked from cord blood and repeated in the neonatal period if breastfed. The baby should also be monitored for clinical signs of abnormal thyroid function for the first few weeks until maternal antibodies and medications have cleared.

Breastfeeding is safe on antithyroid medication in normal doses, but breastfed babies may need more prolonged monitoring for abnormal thyroid function.

Women on long-term T₄ replacement should have T₄ and TSH checked at booking and again in the second and third trimesters if normal. Some women require an increased dose of T₄ in pregnancy but this may represent previous underreplacement prior to pregnancy.

Effect on the fetus

If untreated, hypothyroidism is associated with miscarriage and later fetal loss and low birth weight. If treated, then fetal complications are rare.

T₄ crosses the placenta in very small amounts and, therefore, neonatal thyrotoxicosis is rare. The autoantibodies also cross, but neonatal hypothyroidism is also extremely uncommon.

Asthma

Asthma occurs in 3% of pregnant women. The disease may deteriorate, improve or be unaffected by pregnancy. The pregnancy is not affected by asthma unless the mother is chronically severely hypoxic, which is rare.

Clinical features

Women present with wheeze, cough or shortness of breath, which may be exacerbated by pollen or upper respiratory tract infection.

Examination should look firstly at general appearance. Inability to complete sentences, tachycardia and increased respiratory rate are signs of severe disease. Wheeze should be audible on chest examination and peak expiratory flow rate should be compared with the patient’s normal best value.

Management of asthma is as for the non-pregnant woman and advice should be given about good compliance with medication. Reassurance that there is no evidence of harm to the fetus from bronchodilators or inhaled corticosteroids is important.

Renal disorders

Asymptomatic bacteriuria

Asymptomatic bacteriuria is persistent bacterial colonization of the urinary tract (> 100 000 organisms/ml) without symptoms. The prevalence is up to 15% in pregnant women.

The risk to the mother is pyelonephritis (1.8–28%) and to the fetus is preterm birth (2.1–12.8%).

Diagnosis of asymptomatic bacteriuria is made on MSU culture. Screening by reagent strip for nitrites, leukocytes, blood or protein detects only 50% of cases. Treatment with a 7-day course of antibiotics effectively eliminates bacteriuria and reduces pyelonephritis (relative risk 0.24) and preterm birth (odds ratio 0.6).

Treatment is indicated for both confirmed infections and for suspected infection on the basis of symptoms and more than a trace of proteinuria or positive nitrite or leukocytes on reagent strip testing. Amoxicillin and cefadroxil are effective and safe in pregnancy. Treatment should be continued for 7 days, with repeat MSU culture after completion of treatment. Women should be advised to increase oral fluids, wipe from front to back and pass urine after sexual intercourse to help prevent recurrences. Recurrent UTI indicates further investigation with renal tract ultrasound and prophylactic antibiotics should be considered, such as 500 mg cefadroxil each night.

Pyelonephritis

Pyelonephritis is common in pregnancy due to the dilatation of the ureters and collecting system increasing the chance of ascending infection. Severe UTI with bacteraemia is associated with a risk of miscarriage and preterm labour and should be treated aggressively.

Intravenous antibiotics (amoxicillin, ampicillin or cephalosporins first-line) should be given until the woman has been apyrexial for at least 24 hours and is tolerating oral fluids and antibiotics. Severe pyelonephritis may need additional gentamicin, which must be carefully monitored to avoid potentially ototoxic levels for mother and fetus. Other management includes hydration, analgesia, paracetamol and rest.

Most women improve within 48 hours, though loin pain and malaise often continue for 2–3 weeks. A total antibiotic course of 2 weeks is necessary, with a repeat urine culture after completion.

Chronic renal disease

Chronic renal disease (e.g. glomerulonephritis, reflux nephropathy and diabetic nephropathy) carries risks to the pregnancy and the mother.

Risks to the mother are:

• Deterioration in renal function

• Proteinuria

• Pre-eclampsia.

Risks to the fetus are:

Poor renal function, hypertension or proteinuria predicts poor outcome. If the prepregnancy creatinine is greater than 250 μmol/l, then 50% of women will experience long-term worsening of renal function and at least 50% of babies will have IUGR and prematurity.

Management

The mother should have a baseline 24-hour urinary protein measurement, urea and creatinine measurement and creatinine clearance. These are repeated at intervals depending on the severity of disease. Close monitoring and treatment of hypertension are also essential. Pre-eclampsia may be difficult to diagnose in a woman with pre-existing proteinuria. Fetal growth should be monitored with regular ultrasound scans.

Renal transplant patients generally do well in pregnancy if renal function is normal prior to conception and immunosuppressive therapy is continued throughout pregnancy. Women should be advised to avoid pregnancy for 2 years after transplant as good renal function at that stage predicts very good long-term survival.

Pre-eclampsia, IUGR and premature delivery are all more likely, especially if proteinuria or hypertension is present before pregnancy. MSU should be sent at each visit, as infection is more likely and also likely to damage the transplanted kidney. Renal and liver function as well as haemoglobin should all be closely monitored.

Delivery should be managed according to obstetric indications, with the addition of antibiotic and steroid cover.

Neurological disorders

Anticonvulsant medication is associated with an increased risk of fetal abnormality (7%), which increases further with the number of different medications taken. Typical abnormalities are neural tube defects, orofacial clefts, cardiac defects and dysmorphic features. The fetus does not seem to be adversely affected by maternal fits, if self-limiting, despite transient fetal bradycardias being observed.

Management

Preconceptual management is outlined in Chapter 11. Folic acid 5 mg daily should be continued throughout the pregnancy because of the risk of folate deficiency in the mother as well as neural tube defects in the fetus.

First-trimester ultrasound identifies gross neural tube defects such as anencephaly. Cardiac scan should be arranged at about 18 weeks and detailed anomaly scan at 20 weeks.

Anticonvulsant medication should be continued throughout the pregnancy and emphasis placed on the risk to the mother of persistent fits. If the incidence of fits increases, the dose of anticonvulsants should be increased after checking drug levels.

Vitamin K 10 mg should be taken daily from 36 weeks as anticonvulsants inhibit production of clotting factors and, therefore, increase the risk of cerebral haemorrhage in the fetus and neonate. Babies should also be given intramuscular vitamin K at birth.

Breastfeeding is not contraindicated with anticonvulsants.

Pregnant epileptics should try to shower rather than bath and if bathing have another person present, due to the risk of drowning if a fit occurs.

Differential diagnosis of fits in pregnancy

A fit in the second half of pregnancy should always be assumed to be eclampsia until proven otherwise, by assessment of blood pressure, urinalysis, FBC, urea, creatinine, urate and liver function. Other causes of fits are hypoglycaemia, cerebrovascular accident, pseudoepilepsy and drug or alcohol withdrawal.

Once eclampsia has been excluded, a first fit in pregnancy should warrant further investigation with blood glucose, calcium and magnesium, CT or magnetic resonance imaging and electroencephalogram.

Multiple sclerosis

Multiple sclerosis is a demyelinating condition of the brain and spinal cord affecting about 1 in 1000–2000 people in the UK. It results in a variable clinical picture of neurological symptoms and signs including optic neuritis and limb weakness.

The condition commonly improves in pregnancy, though the relapse rate is 40% after delivery. No specific management is indicated antenatally or for delivery.

Bell’s palsy

Bell’s palsy is a unilateral lower motor neurone disorder affecting the seventh cranial nerve (facial nerve). It causes facial muscle weakness, loss of taste on the anterior two-thirds of the tongue and pain around the ear.

It occurs in 4 in 10 000 pregnancies and is 10 times more common in pregnancy than in the non-pregnant population.

The diagnosis is made on examination. Ramsay Hunt syndrome (varicella-zoster infection of the facial nerve) is the important differential diagnosis, which can be excluded by checking that no vesicles are present in the ear.

Recovery from Bell’s palsy over a few weeks is spontaneous in 90%, but prednisolone 40 mg/day for 1 week speeds recovery if given within the first day of symptoms.

Liver disorders

Obstetric cholestasis

Obstetric cholestasis is a pregnancy-specific condition of impaired bile acid excretion. It has little serious effect on the mother, but is associated with poor fetal outcome. The aetiology is unknown, but it appears to relate to the oestrogen concentration during pregnancy.

Clinical features

Women present with severe itching, especially on the limbs, trunk, palms and soles.

No rash is present unless it is due to excoriation.

Investigations

Liver function tests are deranged in some women (elevated ALT and AST, alkaline phosphatase and gamma glutamyl transaminase). Bile acids are markedly increased and may be the only abnormality on which to confirm the diagnosis, but results can take up to 2 weeks to obtain. Coagulation tests should only be monitored when liver function is abnormal.

If abdominal pain or other features are present, then ultrasound and hepatitis serology should be arranged to exclude other causes of itching and abnormal liver function.

Maternal risks

Vitamin K deficiency and subsequent risk of postpartum haemorrhage have very rarely been reported with obstetric cholestasis.

Effect on the fetus

The main concern with obstetric cholestasis is the risk of sudden intrauterine death, but fetal distress in labour, spontaneous preterm delivery and intracranial haemorrhage can also occur. The fetal outcome cannot be predicted by severity of symptoms in the mother.

Fetal growth, liquor volume and umbilical artery Doppler should be monitored, though these may not help to predict sudden intrauterine death. CTG in labour is also recommended. Delivery is aimed at 37–38 weeks to minimize the risk of intrauterine death without disproportionately increasing the risks of prematurity.

Management involves urgent delivery after correction of blood glucose, clotting factors and hypertension if present. Renal failure and DIC should be treated if they occur. Transfer to a liver unit is usually indicated, or to an intensive care unit if that is not possible. Liver transplant is sometimes performed in severely ill women.

Cardiac disease

The overall incidence of heart disease in pregnancy is about 1%. It is a major cause of indirect maternal death. The commonest problems are atrioseptal defect, ventriculoseptal defect and rheumatic mitral disease (stenosis or incompetence). Pregnancies in these women are generally well tolerated, especially if the defects have been corrected. Cyanotic heart diseases such as Eisenmenger’s syndrome are significantly more difficult to manage in pregnancy, with 30% maternal complication rate, 50% fetal loss rate and significant maternal mortality.

Pathophysiology

The changes in maternal physiology that affect cardiac disease in pregnancy are:

• Increased plasma volume

• Increased cardiac output

• Catecholamine release from pain and anxiety at delivery

• Sudden increase in blood volume at delivery (about 500 ml) as the uterus contracts

• Sudden decompression of the vena cava at delivery.

Heart disease in pregnancy may be practically classified as high-, moderate- or low-risk, according to the severity of the effect on the mother in terms of:

• The degree of cyanosis

• The presence of pulmonary hypertension

• The New York Heart Association functional class (degree of breathlessness/exercise tolerance).

Table 12.8 gives a classification of cardiac disease in pregnancy according to maternal risk.

Table 12.8. Cardiac disease according to maternal risk in pregnancy

High-risk (mortality up to 50%):
Eisenmenger’s syndrome
Tetralogy of Fallot
Transposition of the great vessels
Pulmonary hypertension (primary or secondary)
Ischaemic heart disease
Hypertrophic obstructive cardiomyopathy
Severe aortic stenosis
Moderate-risk (mortality up to 15%):
Valve stenosis
Coarctation of the aorta
History of myocardial infarction
Marfan’s syndrome
Mechanical prosthetic valve
Low-risk (mortality around 1%):
Valve regurgitation
Mitral valve prolapse
Uncomplicated ventriculoseptal defect/atrioseptal defect/patent ductus arteriosus
Porcine valve replacement