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Maternal medicine


Learning Outcomes

After studying this chapter you should be able to:

Knowledge criteria

  • Describe the aetiology, risk factors, 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 pre-conceptual 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

    • Varicosities

    • Carpal tunnel syndrome

Introduction

Maternal medicine encompasses the spectrum of medical conditions a woman can present with in pregnancy. Some of these may pre-date 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 UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2013–15 , venous thromboembolism was responsible for maternal death in 1.13 per 100,000 maternities, whilst cardiac disease was responsible for maternal death in 2.34 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 (CF)) 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.

Multidisciplinary and multi-professional team-working are also essential elements in caring for these women.

Fig. 9.1, Framework for medical disorders in pregnancy.

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 diseases that need 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 and physiological. However, it is important to identify cases where there may be a pathological cause.

The physiological causes include:

  • stretching of the abdominal ligaments and muscles

  • Braxton Hicks (‘practice’) contractions

  • pressure of the gravid uterus on the abdominal contents

  • constipation

It is important to differentiate physiological abdominal pain from pathological causes in women with severe, atypical or recurrent pain. These include:

  • 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

Social causes, particularly domestic abuse, should be considered in women who present with recurrent episodes of abdominal pain where organic pathology has been excluded.

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 (AFLP) and gallstones

Conservative management includes dietary advice to avoid spicy and acidic foods and to avoid eating just prior to bed. Symptoms can be improved by changing sleeping position to a more upright posture. If conservative measures are not successful, antacids are safe in pregnancy and can be used at any time. Histamine-receptor blockers, such as ranitidine, and proton pump inhibitors have a good safety profile in pregnancy and can be used if antacids alone are insufficient to improve symptoms.

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 osmotic and stimulant 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 (DVT) 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 in haemoglobin and red cell parameters in normal pregnancy.

Table 9.1
Haemoglobin and red cell indices (mean and calculated 2.5th–97.5th percentile reference ranges)
Red cell indices Gestation
18 weeks 32 weeks 39 weeks 8 weeks postpartum
Haemoglobin (Hb) g/L 119 (106–133) 119 (104–135) 125 (109–142) 133 (119–148)
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)
Reproduced with permission from Shepard, MJ, Richards VA, Berkowitz RL, et al. (1982) An evaluation of two equations for predicting fetal weight by ultrasound. Am J Obstet Gynecol 142:47–54. © 1982 Elsevier.

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

Risk factors within pregnancy include multiple pregnancy due to the increased iron demand in multiple pregnancy scenarios.

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 100 g/L in the first trimester and less than 105 g/L in the second and third trimesters.

Implications for 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 pre-term birth and low birth weight and possibly greater blood loss at delivery.

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 optimize a woman’s haemoglobin levels in pregnancy and reduce 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. Sometimes a blood transfusion is considered if the anaemia is severe and it is diagnosed close to delivery.

Adequate continued postnatal treatment is essential to reduce the risk of a woman entering a further pregnancy anaemic.

B 12 deficiency is extremely rare in pregnancy, but if it is diagnosed, treatment is with oral or parenteral B 12 supplementation.

Prophylaxis

Routine iron supplementation (usually combined with folic acid) 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 up to 9% of all pregnancies in Western countries. However, the prevalence is much higher in at-risk populations (e.g. Asian or obese women).

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 contributes 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, amended 2015). The guideline only recommends that some of the risk factors be used for screening in practice. The presence of one or more of these risk factors should lead to the offer of a 75-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.

Box 9.1
Women at increased risk of glucose intolerance in pregnancy
From National Institutes for Health and Clinical Excellence (2008, amended and updated 2015). Diabetes in pregnancy: Management of diabetes and its complications from pre-conception to the postnatal period . NICE Publication Guideline NG 63.

  • Previous macrosomic infant (more than 4.5 kg or above) ∗

    ∗ 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.

  • Previous gestational diabetes ∗

  • First-degree relative with diabetes ∗

  • Obesity (BMI more than 30 kg/m 2 ) ∗

  • Specific ethnic family origin with a high prevalence of diabetes ∗ :

    • 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

  • Fasting blood glucose (FBG) more than 6.0 mmol/L or random blood glucose more than 7.0 mmol/L

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 earlier, screening is by a 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.

Table 9.2
Diagnostic criteria for gestational diabetes using a 75-g oral glucose tolerance test
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
IADPSG , International Association of Diabetes and Pregnancy Study Groups; WHO , World Health Organization.
In a given population, use of the IADPSG criteria results in more diagnoses of ‘gestational diabetes’ than using the WHO criteria.

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 BE, Gabbe SG, Persson B, et al. (2010) International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33:676–682.

Implications for 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, with 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.

Table 9.3
Effect of gestational diabetes on pregnancy
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

Whilst for the majority of women gestational diabetes will resolve post-pregnancy, in some women, this diagnosis is the unmasking of type 2 diabetes and diabetic care will need to continue.

Women who have had gestational diabetes remain at higher risk of developing type 2 diabetes later in life. These women should have some form of regular screening, such as annually, to exclude diabetes.

For the babies, fetal programming effects increase the risk of obesity and diabetes in later childhood.

Management

Multidisciplinary 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 pre-prandial/fasting capillary glucose levels should be between 4.0 and 6.0 mmol/L and that the 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.

Vigilance should be maintained for the development of pre-eclampsia.

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. If pre-term delivery is considered, antenatal corticosteroids should be considered to reduce the likelihood and severity of respiratory distress in the newborn. The corticosteroids may necessitate a short-term increase in diabetic treatment to keep blood glucose values in the normal range. 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, acyclovir 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 a worldwide 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 pre-term 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 infection

HIV is a virus that weakens the immune system, and over time AIDS 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 for the disease

Pregnancy does not appear to accelerate the course of HIV infection or increase the chance of AIDS developing.

Implications of the disease for 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 breast-feeding. The risk is highest in advanced disease, at seroconversion and with high viral loads. In women who do not breast-feed, transmission rates fall to less than 25%. With medical intervention in the form of multiple antiretroviral 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.

There is some evidence that the hormonal effects of the pregnancy may increase the risk of toxicity of antiretroviral therapy in the woman, especially the nucleoside reverse transcriptase inhibitors. Side effects reported have included lactic acidosis, hepatic failure and even maternal death. In addition, some antiretroviral agents are thought to be teratogenic and should be avoided in pregnancy.

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 breast-feeding. 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, provided the agents have not been reported to have any toxic effects in the woman or teratogenicity in the fetus. 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 post-exposure prophylaxis for several weeks. Women should be strongly advised not to breast-feed.

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 pre-term 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. Vaccination is not contraindicated during pregnancy. Women at risk of hepatitis B and C should be counselled regarding risk-taking behaviour (particularly intravenous drug use). Hepatitis B immunization can be offered before and during 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 hepatitis 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 (TB) 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 travellers to and from endemic areas. TB and HIV are synergistic. HIV is one of the commonest triggers for TB reactivation, and TB is responsible for about 25% of the deaths in people with HIV. The two main proven 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 routinely in high-risk areas and specifically if the disease is suspected in a patient. 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. Women with proven TB should also be screened for HIV. 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. Pregnancy appears to increase the likelihood of infection. Women who live in endemic areas also 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 infants born to mothers who have immunity, as protective immunoglobulin G (IgG) 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, pre-term 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.

Rubella infection

Rubella (German measles or ‘third disease’) is an exanthematous disease caused by a single-stranded RNA virus acquired via respiratory droplet exposure. After a 2- to 3-week incubation period, symptomatic patients develop a rash, fever, arthralgias and lymphadenopathy. Fifty to seventy-five percent of infected patients manifest clinical features. Severe complications such as encephalitis and bleeding diathesis are rare.

Rubella infection is usually a mild illness in adults and children. However, fetal infection can be severe. Congenital rubella syndrome (CRS) may produce transient abnormalities (e.g. purpura, splenomegaly, jaundice, meningoencephalitis and thrombocytopenia) or permanent abnormalities (e.g. cataracts, glaucoma, heart disease, deafness, microcephaly and mental retardation). Long-term sequelae reported include diabetes, thyroid abnormalities, precocious puberty and progressive rubella pan-encephalitis. Defects involving virtually every organ have been reported.

The rate of fetal infection is highest at 11 weeks and >36 weeks. However, the overall rate of congenital defects is greatest in the first trimester (90%) and declines steadily in the second and third trimesters.

The introduction of rubella vaccine has dramatically reduced the incidence of CRS. The problem should be prevented by childhood vaccination as part of the measles, mumps and rubella (MMR) programme backed up by vaccination programmes for girls in their early teens. However, sporadic cases still occur, especially in women who have not been vaccinated. Thus, ideally women should check their serological status before they conceive and, if negative, they should be offered vaccination. Though the advice is to avoid conception for at least 28 days after vaccination, there is no evidence that vaccination in pregnancy has any effect on the fetus and is not an indication for termination.

In many countries, rubella immunity (indicated by positive serum IgG) status is checked at the first clinic visit for all women. However, in the UK this practice stopped in 2016 because of the low population prevalence of rubella. If a rubella-immune woman is exposed to infection, the absence of the acute marker (serum IgM) by 3 weeks after exposure confirms that she has not been infected and can be reassured. However, if a rubella-susceptible woman is exposed, it is first important to confirm the diagnosis in the index case. The management thereafter will depend on whether the woman develops infection (diagnosed by becoming IgM positive), the stage of pregnancy and the woman’s wishes.

Zika virus infection

Zika virus is a mosquito-borne flavivirus transmitted by Aedes aegypti mosquitoes, which also transmits dengue and chikungunya virus. The mosquitoes are found throughout much of Africa, Asia, the Americas and the Pacific Islands. There has been a rapid spread of the virus and associated illness in humans since 2015, although the first outbreak was reported in 2007. Consequently, there is still much about the virus and its effects that is not understood.

In 2017, a joint RCOG/RCM/PHE/HPS clinical guideline, ‘Zika Virus Infection and Pregnancy’, was published to help health care professionals.

The majority of cases of Zika virus are acquired from infected mosquito bites; however, a few cases of sexual transmission and some through blood transfusions have been reported. Most people (80%) infected with Zika virus have no symptoms. If symptoms do develop, these generally occur 3–12 days following the exposure. Those with symptoms have a mild, short-lived (2- to 7-day) illness comprising rash, pruritus, fever, headache, arthralgia, myalgia, conjunctivitis and lower back pain. These symptoms are similar to those of dengue fever and chikungunya, and patients should be tested for all three organisms. Pregnant women are not more vulnerable to infection, nor do they have a more serious illness. Serious complications in an adult from Zika virus infection are rare, although an increase in triggering of Guillain–Barré syndrome has been reported. Zika virus can be detected by polymerase chain reaction (PCR) of blood within 1 week of symptoms developing. This usually is performed at a national specialist laboratory. Testing of asymptomatic women is generally not recommended unless there are suspected fetal complications (see later).

The main concerns in pregnancy are the fetal implications of Zika virus infection. Some cases of maternal-fetal transmission have been reported.

Following a systematic review of the literature up to 30 May 2016, the World Health Organization (WHO) concluded that Zika virus infection during pregnancy is a cause of congenital brain abnormalities. Abnormalities associated with congenital Zika virus syndrome (CZVS) include a variety of cranial abnormalities (including microcephaly with brain atrophy, cerebral calcification, ventriculomegaly, periventricular cysts, microphthalmia) and extra-cranial abnormalities (including fetal growth restriction, oligohydramnios, talipes). The reported risk of CZVS in Zika-positive pregnancies has varied widely (6–46%). It is not clear whether the risk of maternal–fetal transmission is greater in the symptomatic woman. In women with no evidence of cranial abnormalities on ultrasound scan, it is at present unclear if a positive result predicts a subsequent fetal abnormality or what proportion of neonates born after infection will have symptomatic disease.

No specific antiviral therapy is available for Zika virus infection. Treatment is generally supportive involving rest, fluids, analgesics and antipyretics. In a pregnant woman with laboratory evidence of Zika virus in her serum or amniotic fluid, the options should be discussed in detail with a specialist in fetal medicine and a neonatal specialist. Some women choose to terminate the pregnancy even if there are no fetal abnormalities on ultrasound examination. Others will opt for continuing the pregnancy and having serial ultrasound scans to monitor fetal anatomy and growth through the rest of the pregnancy.

Whilst viable virus has been detected in breast milk, there is currently no evidence that Zika virus can be transmitted to babies through breast milk, and mothers are advised that there is no contraindication to breast-feeding. There is currently no vaccine or drug available to prevent Zika virus infection. It is recommended that pregnant women postpone non-essential travel to areas with high risk of Zika virus transmission until after pregnancy and consider the same for areas with moderate risk of Zika virus transmission. If pregnant women travel to high- or moderate-risk areas, they should take all necessary bite-prevention measures (light-coloured, loose-fitting clothes that cover as much exposed skin as possible, DEET-based insect repellents and sleeping/resting under a mosquito net) and be monitored and/or tested on their return. It is also recommended that women avoid becoming pregnant by using effective contraception while travelling in an area with high or moderate risk of Zika virus transmission and for at least up to 6 months on her return.

Testing of asymptomatic pregnant women is not recommended in the absence of ultrasound-identified fetal microcephaly or other related intracranial abnormalities, but serial fetal ultrasound is recommended.

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 pre-term 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 pre-date pregnancy, can 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

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