After studying this chapter you should be able to:
Knowledge criteria
- •
Describe the aetiology, risk factors for, risks and management of:
- –
Anaemia in pregnancy
- –
Gestational diabetes
- –
Infections in pregnancy
- –
Thromboembolic disease in pregnancy
- –
Liver disease
- –
- •
Contrast the clinical presentation and management of pre-existing medical conditions in pregnancy including:
- –
Diabetes
- –
Obesity
- –
Thrombophilias
- –
Epilepsy
- –
Thyroid disease
- –
Cardiac disease
- –
Respiratory disease
- –
Renal disease
- –
Haemoglobinopathies
- –
- •
Discuss the role of preconceptual counselling for women with pre-existing illness, and the risks and modifications required to continue drug treatment during pregnancy
Clinical competencies
- •
Explain to the mother the causes and plan the management of minor complaints of pregnancy including:
- –
Abdominal pain
- –
Heartburn
- –
Constipation
- –
Backache
- –
Syncope
- –
Varicosties
- –
Carpal tunnel syndrome
- –
Introduction
Maternal medicine encompasses the spectrum of medical conditions a woman can present with in pregnancy. Some of these may predate pregnancy and others may develop during pregnancy. Currently in the UK, with improvements in other areas of obstetric care, most maternal deaths are now caused by medical conditions. In the most recent edition of the Confidential Enquiry into Maternal Deaths (2006–2008) venous thromboembolism was responsible for maternal death in 0.79 per 100 000 maternities, whilst cardiac disease was responsible for maternal death in 2.31 per 100 000 maternities.
There are an increasing number of women with medical conditions in pregnancy. Women with significant pre-existing medical conditions that in the past may have led to voluntary or involuntary infertility (for example, cystic fibrosis) are now becoming pregnant in increasing numbers. In addition, more women are older when embarking on pregnancy and have more acquired problems such as obesity and hypertension.
Whether a woman is known to have a medical condition prior to pregnancy or develops one within pregnancy, the key to successful management is to have a framework to ensure that all the implications of the condition are considered ( Fig. 9.1 ). This enables robust pregnancy plans to be made whether a disease is common or rare. Multi-disciplinary and multi-professional team-working are also essential elements in caring for these women.
Minor complaints of pregnancy
Minor complaints of pregnancy by definition do not cause significant medical problems. However, minor medical complaints are often not perceived as minor by the women affected and can have considerable impact on a woman’s quality of life in pregnancy. In addition, many of the symptoms of minor conditions of pregnancy are the same as those of significant pathological disease that needs to be excluded. Symptoms frequently relate to physiological adaptations of the body to pregnancy and women should be reassured (once pathology has been excluded) that these symptoms represent normal pregnancy changes.
Abdominal pain
Abdominal pain or discomfort is common in pregnancy and is usually transient. The physiological causes include:
- •
stretching of the abdominal ligaments and muscles
- •
pressure of the gravid uterus on the abdominal contents
- •
constipation.
- •
early pregnancy problems such as ectopic pregnancy and miscarriage
- •
gynaecological causes such as ovarian torsion
- •
urinary tract infection
- •
surgical causes such as appendicitis and pancreatitis
- •
later obstetric causes such as placental abruption and labour.
Once a pathological cause has been excluded reassurance is often a successful management option and analgesics are rarely required.
Heartburn
Gastro-oesophageal reflux is more likely to occur in pregnancy because of delayed gastric emptying, reduced lower oesophageal sphincter pressure and raised intragastric pressure. It affects up to 80 % of pregnant women, particularly in the third trimester. The differential diagnoses are:
- •
other causes of chest pain such as angina, myocardial infarction and muscular pain
- •
causes of upper abdominal pain that can mimic reflux, for example, pre-eclampsia, acute fatty liver of pregnancy and gallstones.
Constipation
Constipation is postulated to be more common in pregnancy because of both elevated progesterone levels slowing colonic motility and the pressure of the uterus on the rectum. It is particularly common in the first trimester. It can be exacerbated by oral iron supplements, frequently taken in pregnancy.
Women should be advised to increase their fluid and dietary fibre intake. Most laxatives are safe in pregnancy and can be considered if conservative management is unsuccessful. Rarely, severe constipation can be a cause of unstable lie in late pregnancy by preventing the fetal head from descending into the pelvis.
Backache
Backache is a very common pregnancy complaint especially as pregnancy advances. The commonest cause is a combination of pressure from the gravid uterus causing an exaggerated lumbar lordosis and a hormonal effect on the supporting soft tissues. Differential diagnoses include urinary tract infection, pyelonephritis and early labour.
Physiotherapy review can help by advising on posture and appropriate stretches and exercises. Simple analgesics may be required. Whilst paracetamol and codeine formulations are safe in pregnancy, aspirin and non-steroidal anti-inflammatory medication should be avoided. One disadvantage of codeine is that it can cause constipation.
Syncope
Physiological vasodilatation from the effects of progesterone on the vascular smooth muscle causes a pooling of blood in dependent areas causing postural hypotension that can lead to syncope. Later in pregnancy, caval compression from the gravid uterus can occur (from around 20 weeks gestation), reducing further the venous return to the heart and precipitating hypotension. Whilst syncope in pregnancy is usually benign, if it is recurrent anaemia, hypoglycaemia, dehydration and arrhythmias should be excluded.
Women should be advised to sit for a while prior to standing when getting up from a lying position and to avoid prolonged standing; later in pregnancy lying supine should be avoided to reduce caval compression and supine hypotension. Dehydration should be avoided.
Varicosities
Varicosities in the legs or vulva may worsen or appear de novo because of a combination of pressure on the pelvic veins from the gravid uterus reducing venous return from lower limb veins and the progestogenic effect on relaxing the vascular smooth muscle. Their appearance is usually diagnostic, but if painful then thrombophlebitis and deep vein thrombosis should be excluded.
Elevating the legs while sitting or lying may improve symptoms. The use of compression stockings can both alleviate symptoms and reduce the risk of venous thromboembolism from stasis in the dilated veins. If severe varicosities are present and there are other risk factors for venous thromboembolism, heparin prophylaxis may need to be considered.
Carpal tunnel syndrome
Fluid retention occurs in pregnancy due to increased capillary permeability. This can cause or worsen carpal tunnel syndrome through compression of the median nerve as it travels through the carpal tunnel.
Wrist splints that reduce wrist flexion are usually the mainstay of treatment in the majority of cases. In severe cases steroid injections are occasionally required and can be given in pregnancy. Surgical release of the carpal tunnel ligament is rarely required with pregnancy-related carpal tunnel syndrome as most resolve post-pregnancy.
Pelvic girdle dysfunction (symphyseal pelvic dysfunction, SPD)
Raised levels of relaxin in pregnancy increase joint mobility to allow expansion of the pelvic ring for birth. However, in some women this effect can be exaggerated and cause discomfort either at the symphysis, the hip or at other points around the pelvis; this usually worsens with increasing gestation. Women often describe characteristic pain on walking or standing with tenderness over the pelvic ring. Urinary tract infection should be excluded with anterior pain.
Physiotherapists will advise on exercises to improve stability, techniques for minimizing symptoms during daily activities and positions for birth. A pelvic girdle support may improve symptoms. As with back pain, simple analgesics can be used. The problem usually resolves after pregnancy
Medical problems arising in pregnancy
Anaemia
Anaemia commonly occurs in pregnancy. While in many developed countries it is mild and quickly and easily treated resulting in minimal complications, in some countries it is severe and a major contributor to maternal death.
Aetiology
Pregnancy causes many changes in the haematological system, including an increase in both plasma volume and red cell mass; the former is greater than the latter with the result that a ‘physiological anaemia’ often occurs. There is an increased iron and folate demand to facilitate both the increase in red cell mass and fetal requirements, which is not always met by maternal diet. Iron deficiency anaemia is thus a common condition encountered in pregnancy, particularly in the third trimester. Table 9.1 shows the changes of haemoglobin and red cell parameters in normal pregnancy.
| Red cell indices | Gestation | |||
|---|---|---|---|---|
| 18 weeks | 32 weeks | 39 weeks | 8 weeks postpartum | |
| Haemoglobin (Hb) g/dL | 11.9 (10.6–13.3) | 11.9 (10.4–13.5) | 12.5 (10.9–14.2) | 13.3 (11.9–14.8) |
| Red cell count × 10 12 /L | 3.93 (3.43–4.49) | 3.86 (3.38–4.43) | 4.05 (3.54–4.64) | 4.44 (3.93–5.00) |
| Mean cell volume (MCV) fL | 89 (83–96) | 91 (85–97) | 91 (84–98) | 88 (82–94) |
| Mean cell haemoglobin (MCH) pg | 30 (27–33) | 30 (28–33) | 30 (28–33) | 30 (27–32) |
| Mean cell haemoglobin concentration (MCH) g/dL | 34 (33–36) | 34 (33–36) | 34 (33–36) | 34 (33–36) |
| Haematocrit | 0.35 (0.31–0.39) | 0.35 (0.31–0.40) | 0.37 (0.32–0.42) | 0.39 (0.35–0.44) |
Risk factors
Pre-pregnancy risk factors are those associated with chronic anaemia:
- •
iron deficiency secondary to poor diet
- •
menorrhagia
- •
short interval between pregnancies
- •
presence of anaemic conditions, such as sickle cell disease, thalassaemia and haemolytic anaemia.
Clinical features and diagnosis
Anaemia is often identified as the result of routine full blood count measurements. Some women will present with symptoms such as shortness of breath and lethargy. There is a variation in normal haemoglobin levels in pregnancy and a gradual fall as pregnancy progresses. Anaemia can be diagnosed with a haemoglobin level less than 11 g/dL in the first trimester and less than 10.5 g/dL in the second and third trimesters.
Implications on pregnancy
Iron-deficiency anaemia mainly affects the mother. With mild anaemia the fetus is usually unaffected despite the reduced oxygen-carrying capacity of the mother. However the baby is more likely to have iron deficiency in the first year of life because of a lack of development of fetal iron stores in utero. With severe anaemia there is an increased risk of preterm birth and low birth weight.
The implications to the mother in all trimesters are the risk of developing symptomatic anaemia that can cause fatigue, reduced work performance and an increase in susceptibility to infections. If anaemia persists to the time of delivery, there will be a lack of reserve if significant blood loss occurs. There is a strong association between severe anaemia and maternal mortality. The risk of requiring blood transfusions peripartum is also raised.
Management
Prompt recognition and treatment of developing anaemia optimizes a woman’s haemoglobin levels in pregnancy and reduces the risk of commencing labour anaemic.
Although most anaemia in pregnancy is secondary to iron deficiency, consideration should be given as to whether there is an underlying anaemia condition or if folate deficiency could also be involved. If there is clinical suspicion that iron deficiency is not the cause of the anaemia or if a woman has failed to respond to iron supplementation then the iron status should be assessed by either ferritin or zinc protoporphyrin levels, folate measured and haemoglobin electrophoresis performed to exclude haemoglobinopathies. Oral iron supplementation is recommended as first line treatment. This is better absorbed if taken with ascorbic acid (for example, orange juice) and if tea and coffee are avoided at the time of ingestion. Dietary advice should also be given. Compliance with iron supplementation is often poor due to the side effects of constipation and gastric irritation. If iron is either not tolerated or if improvements in haemoglobin are not seen despite iron therapy then parenteral iron can be considered.
Adequate continued postnatal treatment is essential to reduce the risk of a woman entering a further pregnancy anaemic.
Prophylaxis
Routine iron supplementation throughout pregnancy may reduce the risk of iron deficiency. This is currently not a routine recommendation in the UK due to the lack of evidence of improved outcomes. In some other countries where iron deficiency is common, this is standard practice.
Gestational diabetes
Gestational diabetes is an increasingly common antenatal condition occurring in 2–9 % of all pregnancies.
Aetiology
Pregnancy induces a diabetogenic state. This is predominantly because of increased resistance to the actions of insulin due to the placental production of the anti-insulin hormones (human placental lactogen, glucagon and cortisol), though the increased production of maternal glucocorticoids and thyroid hormones during pregnancy also contribute to this. In response, the maternal pancreas must increase its production of insulin to combat this. In some women this is not achieved and gestational diabetes is the result.
Risk factors
Risk factors are the same as those for type 2 diabetes and are listed in Box 9.1 . This list is taken from the NICE Clinical Guideline ‘Diabetes in pregnancy’ (2008). The Guideline only recommends that some of the risk factors should be used for screening in practice. The presence of one or more of these risk factors should lead to the offer of a75 g oral glucose tolerance test (OGTT). However, many clinicians feel that the presence of any risk factor, rather than a subset, should trigger the offer of an OGTT.
- •
Previous large infant (more than 4.5 kg, or above the 95th centile for gestational age) *
- •
Previous gestational diabetes *
- •
First-degree relative with diabetes *
- •
Obesity (BMI more than 30 kg/m 2 ) * or booking weight more than 100 kg
- •
Specific ethnic background:
- –
South Asian (specifically women whose country of family origin is India, Pakistan or
- –
Bangladesh)
- –
Black Caribbean
- –
Middle Eastern (specifically women whose country of family origin is Saudi Arabia, United Arab Emirates, Iraq, Jordan, Syria, Oman, Qatar, Kuwait, Lebanon or Egypt)
- –
- •
Macrosomia in current pregnancy (variably defined in different studies, e.g., fetal abdominal circumference measured with ultrasound >90th centile, or fetal weight estimated using formulae based on ultrasound measurements)
- •
Glycosuria ≥1+ on more than one occasion or ≥2+ on one occasion
- •
Previous unexpected perinatal death
- •
History of polycystic ovary syndrome
- •
Polyhydramnios
- •
FBG more than 6.0 mmol/L or random blood glucose more than 7.0 mmol/L
Key: Risk factors in bold are those that the NICE Clinical Guideline recommends should be used for screening in practice during pregnancy in the form of a 75 g oral glucose tolerance test.
Clinical features and diagnosis
Gestational diabetes may be asymptomatic. As such, a screening programme needs to be in place that can either be universal or selective. Most units prefer a selective approach for practical and financial reasons. Selective screening is offered to the at-risk groups listed in Box 9.1 . As described above, screening is by an 75 g OGTT at 28 weeks, or if very high risk, early in the second trimester and then repeated at 28 weeks (if normal at the first test). In the OGTT, a fasting glucose level is first measured, then a 75 g loading dose of glucose is given and a further glucose level taken at 2 hours post-sugar load. There is an ongoing debate as to the levels of glucose at which gestational diabetes should be diagnosed. Table 9.2 indicates the two most commonly used diagnostic criteria.
| Diagnostic criteria | Normal fasting value (venous plasma glucose) | Normal 2 hour value (venous plasma glucose) | |
|---|---|---|---|
| WHO 1999 a | One or more abnormal values required | <7.0 mmol/L | <7.8 mmol/L |
| IADPSG b | One or more abnormal values required | <5.1 mmol/L | <8.5 mmol/L |
a World Health Organization: Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications: Report of a WHO Consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus. Geneva, World Health Organization, 1999.
b Metzger, B.E., Gabbe, S.G., Persson, B., et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676–682.
Implications on pregnancy
Gestational diabetes is predominantly a disease of the third and sometimes second trimester ( Table 9.3 ). In the mother, the presence of gestational diabetes increases the risk of recurrent infections and of pre-eclampsia developing. For the fetus there is increased risk of polyhydramnios and macrosomia, the latter being related to the degree of glucose control. There is an increased risk of stillbirth. Considering birth, women with gestational diabetes are more likely to have an induction of labour. If vaginal birth occurs, shoulder dystocia, an instrumental birth and extended perineal tears are more common. Women with diabetes are more likely to have a caesarean section. Babies are more likely to need admission to the neonatal unit. They are at increased risk of neonatal hypoglycaemia due to the relative over-activity of the fetal pancreas in utero. This is less likely to occur if maternal blood sugars are well controlled around the time of birth. Maternal glucose readily crosses the placenta whilst insulin does not.
Remember that glucose crosses the placenta readily and that maternal hyperglycaemia results in elevated blood glucose levels in the fetus. Insulin, on the other hand does not pass across the placenta and therefore the fetus is entirely dependent on the supply of its own insulin production for the regulation of its blood sugar levels.
| Maternal risks/complications | Fetal/neonatal risks/complications | |
|---|---|---|
| First trimester | – | – |
| Second trimester Third trimester | Pre-eclampsia Recurrent infections | Macrosomia Polyhydramnios Stillbirth |
| Labour | Induction of labour Poor progress in labour | |
| Delivery | Instrumental birth Traumatic delivery Caesarean section | Shoulder dystocia |
| Postnatal | Neonatal hypoglycaemia Neonatal unit admission Respiratory distress syndrome Jaundice | |
| Longer term | Type 2 diabetes later in life | Obesity and diabetes in childhood and later life |
Management
Multi-disciplinary teams consisting of obstetricians, diabetic physicians, diabetic specialist nurses and midwives and dieticians should manage diabetes in pregnancy.
Antenatally, the aim is to reduce the risk of complications by achieving good glucose control. Initially, this is by dietary measures aiming to avoid large fluctuations in glucose levels: consuming increased amounts of low glycaemic index carbohydrate and lean protein and avoiding high glycaemic index carbohydrate foods. If this is unsuccessful then medication can be used. Metformin and glibenclamide are increasingly used in pregnancy and may reduce the need for insulin, but a number of women with gestational diabetes will need insulin to optimize control. The aim is that preprandial/fasting capillary glucose levels should be between 4.0 and 6.0 mmol/L and that 2-hour post-prandial value should be between 6.0 and 8.0 mmol/L. Randomized-controlled trial evidence has demonstrated that treatment of gestational diabetes with the aim of achieving normoglycaemia in the woman improves outcomes. Serial growth scans are advised to alert to increasing macrosomia.
Delivery at term is recommended to reduce the risk of stillbirth. This may need to be brought forward depending on the degree of diabetic control, the presence of macrosomia or if other conditions have arisen, such as pre-eclampsia. In labour, blood glucose should be regularly measured and hyperglycaemia treated to reduce the risk of neonatal hypoglycaemia. The fetus should be continuously monitored. Diabetic therapy can be discontinued with the delivery of the placenta. The baby will need blood glucose measurements to look for hypoglycaemia, and feeding should be commenced early to assist the baby in maintaining its sugar level.
Postnatally, all diabetic treatment should be discontinued and capillary glucose testing continued. In the majority of women these values will be normal, indicating that this was genuine gestational diabetes. If they remain elevated then there is a suspicion of type 2 diabetes and referral to a diabetic team is indicated. Women should be advised of the long-term implications of gestational diabetes and the need for regular screening by, for example, an annual OGTT by their general practitioner. Advice on reducing other lifestyle risks associated with diabetes may also be appropriate.
Infections acquired in pregnancy
Women will encounter infections in pregnancy just as they would outside of pregnancy. However, the relative immunosuppressive conditions of pregnancy can affect the way the body responds to the infection.
Risk factors
Pregnant women with small children or who work with children are more likely to come across many infectious conditions.
Implications on pregnancy and management
The implications on pregnancy and management vary depending on the specific infection. Once more, it is vital to consider both the impact on the mother and the fetus. The impact on the fetus can change when the same infection is contracted at different gestations.
Chicken pox
Chicken pox is a highly infectious childhood illness caused by Varicella zoster virus; it has significant implications on both the mother and fetus. Pregnant women are particularly at risk of developing a varicella pneumonia that has a high maternal and fetal mortality rate. If acquired early in pregnancy, there is a 1–2 % risk to the fetus of congenital varicella syndrome (eye defects, limb hypoplasia and neurological abnormalities). If acquired near term there is a risk of neonatal varicella that has a significant mortality risk.
If a non-immune pregnant woman is exposed to chicken pox, she can be offered zoster immunoglobulin to reduce the risk of infection. If a woman becomes infected, aciclovir should be given to reduce the risk of maternal complications. Ultrasound imaging can screen for congenital varicella syndrome. With infection at term, delivery should ideally be delayed to allow time for passive transfer of antibodies to the fetus. Care should be taken to avoid contact with other non-immune pregnant women.
Parvovirus B19
Infection with parvovirus B19 is also known as erythema infectiosum, fifth disease or ‘slapped cheek syndrome’. A common childhood illness, maternal symptoms can include fever, rash and arthropathy, but often effects are minimal. In contrast, there are potentially significant fetal effects as parvovirus infects rapidly dividing cells and can cause miscarriage in early pregnancy and fetal anaemia and heart failure (‘fetal hydrops’) later in pregnancy.
Management includes the use of simple analgesics and antipyretic agents for the maternal symptoms and avoidance of contact with other pregnant women. If the infection is contracted after 20 weeks, serial Doppler ultrasound scanning of the blood flow in the fetal middle cerebral artery can detect fetal anaemia (blood flow increased) that may need to be treated with in utero blood transfusions.
Influenza H1N1
Influenza H1N1 caused world-wide pandemic infection in 2009 and 2010 and is now one of the predominant seasonal influenza virus strains. Pregnant women present with fever and cough similar to non-pregnant individuals. However, pregnant women are at greater risks of complications such as respiratory failure and secondary bacterial infections and have a significantly higher risk of dying than non-pregnant individuals. In addition, implications include an increased risk of preterm birth, stillbirth and neonatal death.
Management includes treatment with antiviral agents, such as oseltamivir or zanamivir, and respiratory support if necessary. All pregnant women should be advised to be immunized against H1N1.
Human Immunodeficiency Virus (HIV) Infection
HIV is a virus that weakens the immune system and over time AIDS (acquired immune deficiency syndrome) may develop. HIV also increases the risk of catching other infections and developing cancers. However, people with HIV infection may be asymptomatic for many years. The number of people living with HIV worldwide is increasing and a significant proportion of these are women of reproductive age. With advancing disease, highly active antiretroviral therapy (HAART) has been shown to reduce morbidity and mortality from HIV infection.
Implications of pregnancy on the disease
Pregnancy does not appear to accelerate the course of HIV infection or increase the chance of AIDS developing.
Implications of the disease on pregnancy
The main concern in pregnancy is the high risk of vertical transmission (up to 45 %) of HIV from mother to baby without medical intervention. This can occur transplacentally in the antenatal period, during vaginal birth and postnatally through breastfeeding. The risk is highest in advanced disease, at seroconversion and with high viral loads. In women who do not breastfeed, transmission rates fall to less than 25 %. With medical intervention in the form of multiple anti-retroviral therapy it is possible to reduce vertical transmission further to less than 2 %.
In addition there are increased risks of miscarriage, fetal growth restriction, prematurity and stillbirth in women with advanced HIV disease.
Some women will already be on HAART prior to pregnancy and this should be reviewed to consider the safety of individual medications in pregnancy. Many women will be treatment naïve.
Women who are taking HAART and have viral loads less than 400 copies/mL can deliver vaginally as there is a very low risk of vertical transmission. However, those who are not taking HAART and/or have viral loads of ≥400 copies/mL or more should be advised to have a caesarean section to reduce the risk of vertical transmission.
Screening
Although many women will know they have HIV when they become pregnant, some women will be unaware that they are HIV positive due to the long asymptomatic stage of the condition. In view of this, the high vertical transmission rate and the efficacy of intervention, many countries now advocate screening in pregnancy. This is usually performed early in pregnancy but in high-risk women it may be appropriate to offer repeat testing later in pregnancy. Women should be fully counselled about the reason for screening for HIV and the improvements in outcome that can be achieved if HIV is diagnosed.
Management
Women with HIV who become pregnant should be managed jointly by a specialist obstetrician and HIV physician. Input from the paediatric team should occur antenatally to discuss neonatal screening and treatment.
Women should be regularly assessed clinically and with blood measurements of viral load and CD4 count.
The initial package of care for women with HIV in pregnancy involves anti-HIV medication, caesarean section and avoiding breastfeeding. The use of anti-HIV drugs in pregnancy has been shown to reduce the risk of vertical transmission. Some women will already be taking HAART for their own health needs and this should continue. In treatment naïve women, anti-HIV medication should commence in the second trimester and continue until birth. Regimes used include zidovudine monotherapy and HAART (nucleotide analogues and protease inhibitors appear relatively safe, non-nucleoside reverse transcriptase inhibitors should be avoided). However, HAART is the recommended treatment of choice. Whilst caesarean section is still advocated for women with non-suppressed disease, women with a viral load of <400 copies/ml who have taken HAART in pregnancy can now opt for vaginal birth without increasing transmission. Invasive procedures should be avoided in pregnancy and labour, for example amniocentesis, the use of fetal scalp electrodes and fetal scalp blood sampling.
Neonatal screening for HIV infection commences at birth and continues until 12 weeks. Babies require neonatal antiretroviral treatment as postexposure prophylaxis for several weeks. Women should be strongly advised not to breastfeed.
Confidentiality is an issue for some women with HIV whose families may not know their status. Women should be reassured that confidentiality can and will be maintained despite the increased medical intervention.
Acute viral hepatitis
Seven hepatitis viruses have been identified, the most common being hepatitis A, B and C. All can present similarly with general malaise, nausea, vomiting and pyrexia together with hepatic dysfunction; however with hepatitis B and C a significant proportion can be asymptomatic (up to 80% of women with hepatitis C). Hepatitis A is spread by the faeco-oral route while B and C are transmitted by a blood-borne route. They can be differentiated by serological tests. Hepatitis A is usually cleared after the initial infection, hepatitis B can be cleared, can persist as a carrier state or can lead to chronic infection, and hepatitis C commonly leads to chronic infection and a long-term risk of cirrhosis and liver failure.
The incidence of hepatitis in pregnancy has a wide geographical variation. In the UK, 1–4% of women will be infected with hepatitis B or C.
Pregnancy does not usually change the course of an acute hepatitis infection. A small number of chronic hepatitis B carriers may suffer a reactivation of the disease state during pregnancy. There is some evidence that pregnancy in women with hepatitis C may cause acceleration of the disease progression.
Hepatitis usually does not impact on the pregnancy itself. In women who have a severe acute infection during pregnancy, there is an increase in the incidence of spontaneous preterm labour. The main concern is the risk of transmission to the neonate. With hepatitis A this can happen if acute infection occurs in the last couple of weeks before delivery. With chronic hepatitis B and C, carriage transmission can occur perinatally. In women with chronic hepatitis C, vertical transmission will occur in 1 in 20 births.
Management in pregnancy relates to prevention, identification and reduction of the risk of vertical transmission. The risk of hepatitis A infection can be reduced by hygiene measures and consideration of immunization for women in areas of endemic hepatitis A infection. Women at risk of hepatitis B and C should be counseled regarding risk-taking behaviour (particularly, intravenous drug use). Hepatitis B immunization can be offered before pregnancy, however there is currently no effective immunization against hepatitis C.
Women can be screened for hepatitis B and C in pregnancy. This may be universal or selective screening based on a woman’s history. Identification antenatally is important to reduce vertical transmission. In women with hepatits C, co-infection with HIV should be excluded.
Vertical transmission of hepatitis B and C is not reduced by either caesarean delivery or avoidance of breast-feeding. Thus vaginal delivery is advocated (unless there are other obstetric indications for caesarean delivery), but with avoidance of interventions that may increase blood contact, such as fetal scalp electrode siting or fetal blood samples. Babies of mothers with hepatitis B can be treated with hepatitis B immunoglobulin and early hepatitis B immunization, which reduces transmission rates to 5–10%. There are limited options to reduce transmission rates with hepatitis C, but early identification of infected neonates ensures adequate follow up for the risk of chronic liver disease.
Tuberculosis
Tuberculosis remains a world health issue with at least 8 million new cases per year and up to 2 million deaths. Although the developed world has low rates of infection, higher rates are found in refugees and travelers to and from endemic areas. The two main risks to the fetus are the use of certain anti-tuberculous drugs and if the mother has severe respiratory illness with sustained hypoxia. Mycobacterium tuberculosis rarely crosses the placenta. The risks to the woman from untreated TB are the same as in non-pregnant patients. Tuberculin testing should be undertaken if the disease is suspected. Chest X-ray and sputum culture should be performed in those who test positive. If the diagnosis is confirmed then multiple therapy, as in the non-pregnant patient, is indicated. Streptomycin is the only drug that is absolutely contraindicated in pregnancy because of the risk of fetal ototoxicity.
Malaria
Malaria occurs in over 200 million people per year and results in more than 1 million deaths annually. It is a common complication of pregnancy in those countries where the disease is endemic. Women who live in endemic areas show an increased prevalence of the severe forms of the disease. The severity of disease is related to the species of parasite, the level of parasitaemia and the immune status of the individual. Plasmodium falciparum is the most virulent of the organisms, as it attacks all forms of the erythrocyte. The parasite grows in the placenta and placental malaria occurs in anywhere between 15 and 60 % of cases. Congenital malaria is rare in the infants born to mothers who have immunity as protective immunoglobulin G crosses the placenta.
The main risk of acute malaria to the woman is severe anaemia and its consequences. In the fetus, acute malaria is associated with an increased likelihood of growth restriction, miscarriage, preterm birth, congenital infection and perinatal death.
Mothers travelling to endemic areas should take prophylaxis or, preferably, not go to the area until the pregnancy is completed. They should also be advised to keep their skin covered and to use insecticides to minimize the risk of being bitten by mosquitoes.
Drug treatment of an acute attack will depend on the nature of the infection. Prophylaxis is given in the form of chloroquine phosphate at a dose of 300 mg each week, starting 1 week before travel and continuing for 4 weeks after leaving the area. Where chloroquine-resistant strains exist, a combination of chloroquine and pyrimethamine with sulfadoxine can be used, or proguanil and mefloquine. These drugs need to be taken with a folic acid supplement. Although chloroquine can cause retinal and cochleovestibular damage in high doses in both the mother and the fetus, it has never been shown to be associated with an increased incidence of birth defects where it has been taken for prophylaxis.
Acute pyelonephritis and urinary tract infections
Asymptomatic bacteriuria occurs in 2–10 % of all sexually active women. When pregnant, 12–30 % of this group of women will develop pyelonephritis from ascending infection due to structural and immune changes to the renal tract. If the bacteriuria is treated with antibiotics, the risk of later development of acute ascending urinary tract infection can be minimized. Nevertheless, approximately 1 % of all pregnancies are complicated by an episode of acute pyelonephritis. The common organism is Escherichia coli and this should be treated aggressively with antibiotics according to known sensitivity. Most community-acquired infections are usually sensitive to amoxicillin or cefuroxime. Additional treatment with fluid replacement, pain relief and bed rest may also be of benefit. Pyelonephritis in pregnancy must not be underestimated as over 15 % of women will develop a bacteraemia, with a small proportion of these progressing to septic shock and/or preterm labour.
Thromboembolic disease
Venous thromboembolism (VTE) is one of the leading causes of maternal mortality in the developed world. VTE is around 10 times more common in pregnancy than when not pregnant.
Aetiology
Pregnancy is a prothrombotic state. Coagulation factors increase, endogenous anticoagulants decrease and fibrinolysis is suppressed. These effects commence in the first trimester and last until a few weeks following birth. In addition venous stasis occurs in the lower limbs from compression on the pelvic vessels further exacerbating the problem.
Risk factors
Risk factors can predate pregnancy, occur as a result of obstetric conditions or can be transient. They include:
- •
pre-existing risk factors:
- ▪
a personal or family history of VTE
- ▪
thrombophilias, obesity, cigarette smoking, some medical conditions (such as sickle cell disease), gross varicose veins and increased maternal age
- ▪
- •
transient risk factors:
- ▪
episodes of immobility and dehydration
- ▪
ovarian hyperstimulation
- ▪
surgical procedures
- ▪
- •
obstetric risk factors:
- ▪
multiple pregnancy
- ▪
pre-eclampsia
- ▪
operative delivery.
- ▪
Clinical features and diagnosis
VTE presents as in non-pregnant individuals: deep vein thrombosis (DVT) with swelling and tenderness of a leg and pulmonary embolism (PE) with respiratory symptoms (shortness of breath and pleuritic chest pain) or collapse. In pregnancy, DVT is more likely to occur on the left (90 %) due to compression of the left common iliac vein by the right common iliac artery and ovarian artery (the vein is not crossed on the right). The majority of DVTs in pregnancy occur in the ileofemoral veins, so lower limb symptoms may not be as obvious. Clots in the ileofemoral veins are more likely to embolise than those in the calf.
d -Dimer measurements are of limited help in pregnancy, although the negative predictive value is high, a positive result does not help to establish a diagnosis as it can increase with the physiological changes in the coagulation system that occur in pregnancy.
Radiological investigations should be performed as in non-pregnant individuals. Doppler ultrasound of the lower limb veins or MRI of the pelvic veins should be performed to assess for DVT. Spiral artery CT or venous perfusion scanning are used to diagnose PE. Although care must be taken when undertaking radiological examinations in pregnancy because of the radiation risk to the fetus, ultimately if an investigation needs to be done to establish a diagnosis it should be done.
Implications on pregnancy
Antenatally, if VTE is adequately treated there are minimal direct effects to mother or fetus. The main implications to pregnancy relate to the medications used to treat VTE (see below). Postnatally, the risk remains high and therapy will need to continue for a number of weeks.
Management
All women should have an individual risk assessment undertaken for VTE in pregnancy. Depending on the risk score, a plan for thromboprophylaxis can be made to reduce the risk of thrombosis occurring. For women with low risk this may not require additional measures; for some women postnatal prophylaxis may be required and for those at highest risk antenatal prophylaxis may be recommended with graduated elastic compression stockings and low molecular weight heparin (LMWH). In this last scenario, thromboprophylaxis should be started as early as possible in pregnancy.
If acute VTE occurs in pregnancy, prompt management is vital and heparin therapy should be commenced empirically whilst awaiting investigations. If a DVT or PE are excluded on subsequent diagnostic testing (see above) then the heparin can be discontinued.
LMWH has been used extensively in pregnancy as it does not cross the placenta and has a good safety profile. In contrast, warfarin crosses the placenta and is associated with an embryopathy if used in the first trimester and with fetal intracranial bleeding when used in the third trimester. Most women with venous thromboembolism can be adequately managed on LMWH so warfarin is rarely needed in this scenario. On most occasions heparin therapy can be temporarily stopped around the time of birth to reduce the risk of postpartum haemorrhage and to enable regional anaesthesia to be given if required (LMWH use is associated with epidural haematoma). Simple measures such as avoiding dehydration and using graduated elastic compression stockings should also be employed.
Postnatally, women traditionally continue on heparin prophylaxis or treatment for 6 weeks. If an acute venous thromboembolic event has occurred in this pregnancy it is likely that heparin prophylaxis will be needed in future pregnancies. Women should also be advised to avoid oestrogen-containing contraceptives.
Liver disease
Obstetric cholestasis
Aetiology
The exact aetiology of obstetric cholestasis is uncertain; however, there appears to be a genetic predisposition to sensitivity to oestrogen which causes abnormalities in liver function.
Risk factors
Certain ethnicities (South American and South Asian) and a past history of obstetric cholestasis are the predominant risk factors for obstetric cholestasis.
Clinical features and diagnosis
Obstetric cholestasis presents with intense itching, especially on the palms of the hands and soles of the feet in the second or third trimester. There is rarely a rash associated with the itching, but excoriation marks are frequently present. Rarely, pale stools, dark urine and jaundice are noted. The diagnosis is confirmed by a rise in bile acids or raised liver transaminases where other pathology (auto-immune disease, gallstones and viral infection) has been excluded.
Some women experience similar symptoms when taking the combined oral contraceptive pill or in the second half of the menstrual cycle.
Implications on pregnancy
Antenatally, the pruritus can be debilitating giving minimal rest, especially at night. The impact on other liver functions can result in a prolongation of blood clotting time. For the fetus there is a small increase in the risk of stillbirth. The risk of preterm birth is higher but this is predominantly due to early induction of labour. The implications for labour and delivery are minimal, but meconium is more likely to be passed in preterm fetuses with obstetric cholestasis.
Obstetric cholestasis has a high recurrence rate (over 90%) in future pregnancies.
Management
The pruritus of obstetric cholestasis can be difficult to treat. Topical emollients are safe for use in pregnancy but provide little symptomatic relief. Antihistamines are sometimes used for their sedative ability but have little impact on the itch itself. Ursodeoxycholic acid has been shown to improve both pruritus and liver function, but long-term safety data is lacking. In spite of this it is the mainstay of antenatal treatment. In view of the potential risk of clotting abnormalities, oral water-soluble vitamin K supplementation can be used, particularly for those women whose clotting tests suggest an abnormality.
The best way to monitor the fetus antenatally has not yet been established. Methods such as serial growth ultrasound scans and cardiotocographs (CTGs) that can detect problems with placental function are not predictive of at-risk fetuses in obstetric cholestasis. Consequently delivery once fetal maturation is reached is often recommended to reduce the small risk of late stillbirth.
Postnatally, women are usually advised to avoid oestrogen-containing contraceptives which can precipitate further symptoms.
Acute fatty liver of pregnancy
Aetiology
Acute fatty liver of pregnancy (AFLP) is a rare but serious condition of pregnancy. The aetiology is uncertain but it shares many characteristics with severe pre-eclampsia and HELLP syndrome (haemolysis, raised liver enzymes and a low platelet count) and is postulated to be a variant of pre-eclampsia.
Risk factors
First pregnancy, multiple pregnancy and obesity are all risk factors.
Clinical features and diagnosis
AFLP usually presents in the third trimester with non-specific symptoms of nausea, vomiting, abdominal pain and general malaise. Jaundice may also be present and women can rapidly deteriorate with liver failure, renal impairment and coagulopathy. Liver and renal function tests are usually deranged and hypoglycaemia may be present.
Implications on pregnancy
The condition is associated with high maternal and fetal mortality. Maternal death occurs secondary to hepatic encephalopathy, haemorrhage and disseminated intravascular coagulation.
Management
Management must be multi-disciplinary with support from critical care professionals. Initial management is supportive to correct the abnormalities present. Once the woman is stable, delivery should be expedited. Dialysis may be necessary postnatally; rarely, liver transplantation is required.
Information regarding recurrence rates is sparse given the rarity of the condition, but is suggestive of an increased chance of recurrence.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
