Chapter 9 Obstetric conditions

Abdominal pain in pregnancy

Amniotic fluid embolism

Antepartum haemorrhage

Cancer in pregnancy

Fibroids in pregnancy

Obstetric cholestasis

Ovarian cysts in pregnancy

Postnatal depression

Puerperal psychosis

Pre-eclampsia and eclampsia

Premalignant conditions of the genital tract in pregnancy

Preterm Labour

Preterm prelabour rupture of membranes

Prolonged pregnancy

Puerperal sepsis

Abdominal pain in pregnancy Epidemiology

This is an extremely common condition in pregnancy.

The commonest obstetric complications manifesting with abdominal pain are spontaneous preterm labour, placental abruption, and severe pre-eclampsia. Pyelonephritis occurs in 1–2% of pregnancies.

Acute abdomen of non-obstetric aetiology requiring surgery has an incidence of 1 in 500–635 pregnancies. The leading cause in this group is acute appendicitis. Aetiology

Although obstetricians and gynaecologists are trained in the recognition and management of the majority of the following conditions, some of the less common causes will require multidisciplinary input.

Physiological

• Labour.

• Musculoskeletal pain from ligament stretching affects about 30% of pregnancies, and is more common in early and late gestation.

• Constipation can be physiological due to decreased bowel motility and increased water absorption of water; if severe, it can become pathological. This is usually amenable to conservative treatment and dietary advice, although bulking agents and in some cases stool softeners or laxatives are needed.

Early pregnancy

• Ectopic pregnancy

• Corpus luteum haemorrhage

• Miscarriage

• Acute urinary retention

• Urinary tract infection.

Second trimester onwards

• Preterm labour

• Chorioamnionitis

• Placental abruption

• Severe pre-eclampsia and HELLP syndrome

• Acute fatty liver of pregnancy

• Uterine rupture/scar dehiscence

• Degenerating fibroid

• Musculoskeletal.

Non obstetric causes

• Ovarian torsion

• Acute pyelonephritis or hydronephrosis

• Urolithiasis

• Gastroenteritis

• Appendicitis

• Bowel obstruction

• Inflammatory bowel disease (ulcerative colitis and Crohn’s disease)

• Biliary colic or cholecystitis

• Pancreatitis

• Pleurisy

• Sickle cell crisis

• Malaria.

Postpartum

• Endometritis

• Postoperative wound infection or haematoma

• Pseudo-obstruction (Ogilvie syndrome) Clinical approach

Interpretation of clinical findings should always take into account anatomic, physiological, and biochemical considerations that are unique to the pregnant woman. Diagnosis

History

Any type of abdominal pain prior to ultrasound confirmation of pregnancy location should prompt consideration of an ectopic gestation. Acute epigastric pain in mid to late gestation should be interpreted in association with any other symptoms and signs of pre-eclampsia (headache, visual disturbance, hyper-reflexia). It is important to remember that HELLP syndrome may also manifest post-partum. Painful uterine contraction is the cardinal symptom in spontaneous preterm labour (intermittent) and placental abruption (continuous). Specific symptoms of non-obstetric abdominal pathology should also be sought.

Examination

The presence of a gravid uterus may alter considerably the findings of abdominal examination. The adnexa remain in proximity to the uterus, lateral and posterior to the fundus and are progressively pulled out of the pelvis and into the maternal abdomen. The appendix is usually displaced upwards to the level of the iliac crest. Abdominal guarding and rigidity may not be a reliable sign of intra-abdominal inflammation because of interposition of the growing uterus.

The presence of uterine activity is best assessed with direct palpation for several minutes. Intermittent contraction may be a sign of labour whereas a continuous contraction with uterine tenderness may suggest placental abruption. Renal tenderness should be tested on both loins. Speculum and digital vaginal examination should be performed if labour is suspected.

Investigations

Blood inflammatory markers should be interpreted with caution: baseline white cell count is raised in pregnancy (6.0–16.0 ? 10⁹/L) and may rise even further (to around 20.0 ? 109/L) following administration of corticosteroids or with the onset of labour. C-reactive protein (CRP) is a more reliable marker of inflammation.

• MSU for dipstick and culture

• 24 hour urine collection for total protein

• CRP

• FBC, U+Es, LFTs, LDH, uric acid, and coagulation screen in suspected pre-eclampsia

• Kleihauer–Betke test may be useful in suspected mild abruption with no fetal compromise

• Fetal fibronectin in vaginal secretions has a good negative predictive value for preterm labour

• Serum amylase

• Arterial blood gases for the critically ill patient.

Imaging

Ultrasound is the modality of choice. Ionizing radiation may be used when benefits outweigh the risks, especially beyond the first trimester.

• Obstetric ultrasound often does not identify the cause of pain. It is however useful as a non-invasive test of fetal wellbeing

• Abdominal ultrasound

• adnexal pathology

• liver, gallbladder, bile ducts

• kidneys, ureters

• bladder residual post micturition

• Transvaginal ultrasound for cervical length in suspected preterm labour

• Plain abdominal X-ray if there is suspicion of bowel obstruction

• MRI or CT if indicated (usually in consultation with other disciplines, i.e. general surgery, urology, radiology) Management

Conservative management

In cases requiring hospitalization intravenous rehydration, analgesia, and antiemetics are the mainstay.

Inflammatory causes

Broad-spectrum antibiotic treatment including anaerobic cover is necessary in cases of septic miscarriage and chorioamnionitis. A history of prelabour rupture of the membranes (PROM) should raise the index of suspicion, but chorioamnionitis can also occur with no history of PROM. Treatment with antibiotics should not delay the decision for delivery of the fetus regardless of gestational age, as the maternal condition can deteriorate rapidly and severely. Antibiotic treatment is also used for cholecystitis and post-partum endometritis or wound infection. Pyelonephritis usually responds to intravenous cephalosporins, with the addition of aminoglycoside in severe cases. Gastroenteritis is often viral and responds to conservative measures alone. Degenerating fibroids may require large doses of opioid analgesia.

Urological causes

Urine retention at 12–16 weeks because of a gravid retroverted uterus can be resolved with catheterization. Pyelonephritis should be treated aggressively with intravenous antibiotics as above. Ureteric obstruction and hydronephrosis may sometimes necessitate percutaneous nephrostomy or retrograde ureteric stenting.

Pre-eclampsia and HELLP syndrome

Clinical and biochemical evidence of severe pre-eclampsia with acute epigastric pain should trigger a protocol of intensive obstetric care. This should include blood pressure control with antihypertensives, seizure prophylaxis with magnesium sulphate, fluid restriction, frequent monitoring of haematological and biochemical profile, and planned delivery. Acute epigastric pain and HELLP syndrome may also present postpartum.

Fatty liver of pregnancy

Much less common than HELLP syndrome, it is associated with pre-eclampsia in only 50% of cases. Quick progression to hepatic and renal failure as well as DIC often warrants management in an intensive care setting.

Preterm labour

Corticosteroids to aid fetal lung maturation should be considered at 24–34 weeks’ gestation.

Placental abruption

Management should be dictated by maternal and fetal condition and the progress of labour. Delivery of fetus may need to be expedited if there is fetal compromise. Antepartum, postpartum haemorrhage, and DIC are potential complications that require haemodynamic monitoring of the mother and prompt resuscitation with intravenous fluids and/or blood products.

Pancreatits

More than half of the cases are gallstone related. Management and monitoring is identical as in the non pregnant state.

Postpartum pseudo-obstruction (Ogilvie syndrome) Intravenous rehydration and nasogastric suction are necessary. Abdominal X-rays to monitor colonic diameter are indicated. Gross distension at around 9–12 cm is a sign of impending perforation. Colonic decompression with colonoscopy may be attempted. Rarely a caecostomy may be necessary.

Surgical management

Laparoscopy

This is the treatment of choice for ectopic pregnancy in the stable patient. Salpingectomy can be performed if the contralateral tube is healthy. Salpingostomy may be preferable if the contralateral tube is damaged or absent. Following laparoscopic salpingostomy β-hCG levels should be monitored as there is an 8% chance of persistent trophoblast.

Laparoscopy in the first trimester may also be necessary in cases of suspected ovarian torsion. Salpingoophorectomy has been traditionally advocated. However, several case reports and case series now support the option of detorsion and sparing of the affected ovary even in the presence of blue-black ischaemic changes.

Advanced gestation has traditionally been considered a contraindication for laparoscopy. However, recent case series suggest that this may be a safe option in experienced hands, even in the third trimester. Open laparoscopic entry (Hasson technique) or Veress needle insufflation at the midclavicular line below the left costal margin (Palmer’s point) may be safer techniques in the presence of a large gravid uterus.

Laparotomy

Laparotomy is the treatment of choice for the acute surgical abdomen at any gestation when conservative treatment fails. Typical examples include open appendicectomy, cholecystectomy in cases of severe or recurrent cholecystitis, and laparotomy for bowel obstruction. It is also the most expedient treatment of ruptured ectopic gestation when the patient is haemodynamically compromised.

If laparotomy needs to be performed electively (large ovarian cyst) it is best performed in the early second trimester when the uterus is smaller and the risk of preterm delivery is reduced.

Delivery of fetus

In advanced pregnancy the decision to deliver the fetus in the course of managing severe abdominal pain emergencies may be based at any of the following considerations:

• delivery in order to optimize the resuscitation and cardiorespiratory stabilization of a critically ill mother

• in the stable mother, because of fetal compromise (abruption)

• in order to terminate the underlying pathological process (i.e. pre-eclampsia, acute fatty liver of pregnancy). Further reading

Augustin G, Majerovic M. Non-obstetrical acute abdomen during pregnancy. Eur J Obstet Gynecol Re-prod Biol 2007;31:4–12.

Sivanesaratnam V. The acute abdomen and the obstetrician. Baillières Best Pract Res Clin Obstet Gynaecol 2000;14:89–102.

Sharp HT. The acute abdomen during pregnancy. Clin Obstet Gynecol 2002;45:405–13.

Nelson-Piercy C. Handbook of obstetric medicine, 3rd edn. Informa Healthcare 2006. Internet resources

www.emedicine.com (needs free registration) Patient resources

www.babycenter.com/0_abdominal-pain-during-pregnancy_204.bc

Amniotic fluid embolism Definition

Amniotic fluid embolism (AFE) or ‘anaphylactoid syndrome of pregnancy’ is a life-threatening obstetric emergency that is characterized by acute hypotension or cardiac arrest, acute respiratory arrest (hypoxia), or coagulopathy occurring during labour, Caesarean section or evacuation of retained products of conception or within 30 minutes postpartum, in the absence of any other potential explanation for the symptoms and signs observed.

It continues to cause significant maternal and fetal morbidity and mortality and remains an unpredictable, unpreventable, and a rapidly progressive disorder. Epidemiology

True incidence of AFE is unknown and about 10-fold variation in estimated incidence has been reported. Estimated incidence varies between 1 in 8000 and 1 in 30 000 pregnancies. Maternal mortality has been reported to be about 80%. However, recently, with advances in intensive supportive therapy, the maternal mortality has been estimated to be between 16% and 30%. Recently, the UK Obstetric Surveillance System (UKOSS) has reported a case fatality rate of 17% for AFE. Recent Confidential Enquiries into Maternal and Child health (Vlies 2007) reported a mortality rate of 25%. Approximately 50% of women who die because of AFE do so within the first hour of onset of symptoms and about 50% of those who survive this acute ‘cardiorespiratory’ phase, develop coagulopathy later. Although, early recognition and aggressive supportive therapy has reduced maternal mortality, many women (7%) sustain permanent neurological damage. The US and UK amniotic fluid registers have reported neonatal survival rates of 79% and 78%, respectively.

AFE exclusively occurs in women and does not have any racial predisposition. Although it was earlier suggested that ‘older, multiparous’ women were more susceptible, recent data from the UK amniotic fluid register does not substantiate this. Pathophysiology

Exact aetiopathogenesis is still unknown. It has been postulated that amniotic fluid and fetal cells, lanugo, hair, etc., enter the maternal circulation and are carried to distant sites (e.g. lungs). Occlusion of pulmonary vasculature may result in symptoms similar to pulmonary venous thrombo embolism. These ‘fetal materials’ may also possibly trigger an anaphylactic reaction to fetal antigens. This may result in mast cell degranulation leading to the release of histamines and other mediators like tryptase as well as activation of the complement pathway. It is not always possible to identify fetal material or components of amniotic fluid in maternal circulation in patients with AFE, and conversely, material of fetal origin is often found in patients with no evidence of AFE.

Once the maternal system is exposed to a ‘trigger’ from the fetoplacental unit, usually there are two phases of pathophysiological response. Phase I is characterized by intense pulmonary artery vasospasm with pulmonary hypertension resulting in hypoxia and elevated right ventricular pressure. This acute hypoxic insult leads to myocardial and pulmonary capillary damage, left ventricular failure, and acute respiratory distress syndrome. Acute hypoxia may also trigger seizures. If this early Phase 1 is not managed appropriately by supportive measures, the mortality is very high.

Phase II is a ‘haemorrhagic phase’ that usually follows the early hypoxic phase (Phase 1) and is characterized by disseminated intravascular coagulation (DIC) leading to massive obstetric haemorrhage, bleeding from the skin and mucosal surfaces as well as into internal organs. Associated uterine atony, possibly due to the toxic effects of fibrin degradation products (FDPs) on myometrium, often worsens existing obstetric haemorrhage due to coagulopathy. FDPs can also depress the myocardium leading to ‘pump failure’. The margin between Phases 1 and II may not be always well demarcated and some women may in fact present with massive coagulopathy. Clinical approach

Symptoms and signs

AFE is unpredictable and is considered to be unpreventable and hence, should be clinically suspected when there is any sudden, unexpected collapse during late pregnancy, labour (oxytocin augmentation, precipitous labour), Caesarean section, obstetric procedures such as evacuation of retained products of conception or amniocentesis or amniofusion or within 30 minutes of these. Classical symptoms and signs include sudden onset of breathlessness with or without cyanosis, cough, altered level of consciousness with or without tonic, clonic seizures, acute hypotension, evidence of pulmonary oedema as well as fetal bradycardia. These are usually followed by evidence of consumption coagulopathy.

Investigations

Full blood count (FBC), clotting profile, liver and renal function tests to exclude other possible causes, chest X-ray (pulmonary oedema), and electrocardiograph (ECG) may show ST segment changes and evidence of right ventricular strain. Pulse oximetry and arterial blood gases (ABG) are useful to determine the degree of hypoxia. Pulmonary artery catheter to estimate the wedge pressure is useful in supportive management

Diagnosis

It has been recommended that the following four criteria should be met prior to making a clinical diagnosis of AFE:

• acute hypotension or cardiac arrest

• acute hypoxia (breathlessness, cyanosis, seizures)

• evidence of DIC or massive haemorrhage in the absence of other possible explanations

• All of these occurring during labour, Caesarean section, evacuation of retained products of conception or within 30 minutes postpartum with no other possible explanation for these findings. Management

Once the diagnosis AFE is made, a multidisciplinary approach should be employed with input from anaesthetists, haematologists, physicians, and intensive therapists to optimize the outcome. Patients often require admission to an intensive treatment unit (ITU) for multi-organ support.

Supportive treatment

This involves maintenance of airway, breathing, and circulation. If the patient has ‘collapsed’, cardiopulmonary resuscitation (CPR) may be required and this should be with a left lateral tilt to reduce the compression of the inferior vena cava by the gravid uterus. Oxygen should be administered via a facemask and if necessary, the patient should be intubated to allow adequate ventilation. Acute hypotension should be aggressively treated with crystalloids and colloids. Massive haemorrhage necessitates replacement of blood and blood products.

Specific treatment

Inotropes such as digoxin may need to be administered in cases of myocardial pump failure to improve cardiac output. Dopamine infusion may help to improve renal perfusion as well as to improve myocardial contractility. Coagulopathy should be aggressively treated with blood transfusion and blood products such as platelets, cryoprecipitate and Recombinant Factor VII.

Obstetric treatment

Management of massive of postpartum haemorrhage requires oxytocics such as oxytocin bolus, infusion, prostaglandin-F2-α, and rectal misoprostol to control bleeding. Algorithms such as ‘HAEMOSTASIS’ have been proposed to aid logical and systematic approach to the management of atonic postpartum haemorrhage and may help clinicians to adopt a stepwise approach. Rarely, if the patient has sustained a cardiorespiratory arrest prior to bleeding and efforts to resuscitate are unsuccessful, a perimortem Caesarean section should be performed within 5 minutes of cardiac arrest. This is done to resuscitate the mother but is also likely to help in fetal salvage. This will reduce compression of the aorta and inferior vena cava by the gravid uterus and, thereby, would help improve venous return and cardiac output. Delivery of the baby is likely to reduce the oxygen consumption by the fetoplacental unit and improve the oxygenation of the mother.

AFE with cardiorespiratory arrest is an unpredictable and unpreventable obstetric emergency. Owing to the high maternal mortality, many cases are diagnosed by a post-mortem examination confirming histological evidence of components of amniotic fluid in the maternal lungs. However, a high index of suspicion is required to make a clinical diagnosis. Familiarity with adult resuscitation and ‘maternal collapse drills’ as well as regular skills and drills training in the management of massive obstetric haemorrhage and a multidisciplinary approach are likely to improve outcome. Further reading

Clarke SL, Hankins GD, Dudley DA, et al. Amniotic fluid embolism: analysis of the national registry. Am J Obstet Gynecol 1995;172:1158–69.

Gilbert WM, Danielsen B. Amniotic fluid embolism: decreased mortality in a population-based study. Obstet Gynecol 1999;93:973–7.

Lim Y, Loo CC, Chia V, Fun W. Recombinant factor VIIa after amniotic fluid embolism and disseminated intravascular coagulopathy. Int J Gynaecol Obstet 2004;87:178–9.

O’Shea A, Eappen S. Amniotic fluid embolism. Int Anesthesiol Clin 2007;45:17–28.

Tuffnell DJ. Amniotic fluid embolism. Curr Opin Obstet Gynaecol 2003;15:119–22.

Tuffnell DJ. United kingdom amniotic fluid embolism register. Br J Obstet Gynaecol 2005;112:1625–9.

UKOSS. Amniotic fluid embolism. In: United Kingdom Obstetric Surveillance System (UKOSS). Oxford: National Perinatal Epidemiology Unit 2008.

Vlies R. Amniotic fluid embolism. In: Saving mothers’ lives: reviewing maternal deaths to make motherhood safer 2003–2005. London: CEMACH 2007: Chapter 5. www.cemach.org.uk

Antepartum haemorrhage Definition

Antepartum haemorrhage (APH) is bleeding from the genital tract from the time of viability of pregnancy for extra uterine survival to the time of delivery of the baby. Incidence

APH occurs in 3.5% of all pregnancies.

The incidence varies with age, parity, and social class.

In approximately half of all women presenting with APH, a diagnosis of placental abruption or placenta praevia will be made; no firm diagnosis will be made in the other half even after investigations. Causes

• Placenta praevia

• Placental abruption

• Antepartum haemorrhage of indeterminate origin

• Vasa previa

• Show

• Bleeding from the lower genital tract:

• vaginal infection/cervicitis

• vulvovaginal varicosities

• tumours

• trauma. Prognosis

Major APH is a significant cause of perinatal morbidity and mortality. It is also a cause of maternal morbidity and mortality.

Minor APHs cause significant maternal anxiety especially if no cause is found. Management

Management of any patient with bleeding in late pregnancy should be in a hospital with facilities for blood transfusion, Caesarean delivery, neonatal resuscitation and intensive care.

Key points in the management of APH

• APH is largely unpredictable and a patients condition may deteriorate rapidly

• Priority is to resuscitate the mother

• Establish fetal viability and wellbeing

• Digital assessment of the cervical dilataion is contraindicated unless placenta previa has been excluded. History

• Gestation and parity

• Amount and character of bleeding

• Association of abdominal pain and uterine contractions

• History of rupture of membranes or previous vaginal bleeds

• Presence and nature of fetal movements

• History of trauma or recent coitus

• Information from scan on placental site. Examination

• General assessment of patient: distressed, pale, unconscious

• Maternal pulse, blood pressure, and respiratory rate

• Abdominal examination: fundal height, presence of tenderness and uterine contractions, fetal lie and presentation

• Vaginal assessment: if placenta praevia has not been excluded then vaginal examination is contraindicated. If placenta praevia has been excluded then speculum examination of the cervix is useful to exclude cervical causes.

• Fetal assessment with cardiotocography (CTG) or ultrasound. Investigations and immediate management

This will obviously depend on the severity of the bleeding and the condition of the mother:

• i.v. access with wide bore cannula

• blood for FBC, group and save or cross-match if heavy blood or evidence of compromise

• if abruption is suspected, coagulation screen and urea and electrolytes.

• i.v. fluids

• if fetal demise with diagnosis of abruption, a significant intrauterine bleed should be anticipated and hence consider blood transfusion.

Subsequent management

This will depend on the condition of the patient and fetus, the amount of bleeding and the likely cause: expectant management if no sign of maternal or fetal compromise

• immediate delivery if maternal or fetal compromise

• individualized management in cases of intrauterine death

Placental abruption (see Chapter 10.12).

Placenta praevia (see Chapter 10.13). Antepartum haemorrhage of indeterminate origin

The exact cause of bleeding in late pregnancy remains unknown in about half of cases of antepartum haemorrhage. The woman typically presents with painless vaginal bleeding without ultrasound evidence of placenta praevia. Placenta praevia can be excluded by an ultrasound scan, but the diagnosis of placental abruption is based on clinical signs and symptoms, and is difficult to confirm in mild cases. Perinatal morbidity is increased in these cases.

In some cases there is separation of a normally sited placenta from its margin leading to bleeding from the marginal sinuses. The pregnancy continues as normal however there may be repeated small bleeds.

Investigations

Speculum examination will exclude local causes. Ultrasound shows a normally situated placenta and a possible retroplacental clot at its margin

Management

Management is largely conservative.

Key points

• 15–20% women presenting with APH without a firm cause labour and deliver in the next 2 weeks. Steroids should be considered if the gestation is Early delivery may need to be planned to initiate treatment: a decision on mode of delivery can generally be made for normal obstetric indications.

The risks of treatment on the children and their subsequent development

• There is no consistent information to suggest an excess of long-term developmental or malignant morbidities for children exposed to antineoplastic agents in utero.

• There is however evidence of long-term deleterious effects on intellectual development and a small increase in secondary malignancies in children exposed to radiation above threshold doses.

• The long-term reproductive ability of children exposed to chemo- or radiotherapy is largely unknown, although some offspring in the largest series studied have reproduced successfully.

Conclusion

All the above data are based on small numbers and mainly retrospective data, although it is generally reassuring concerning general prognosis and treatment. No clinician will see many of these cases and therefore each case needs to be managed on an individual basis and the development of registers for pregnant cancer patients may help to inform international experience. Further reading

Hayes K. Cancer and its management in pregnancy. JPOG 2006: 149–55.

Cardonik E, Iacobucci A. Use of chemotherapy during human pregnancy. Lancet Oncol 2004;5:283–91.

Weisz B, Meirow D, Schiff E, et al. Impact and treatment of cancer during pregnancy. Expert Rev Anticancer Ther 2004;4:889–902.

Lewis G, Drife J (eds). Saving mothers lives. confidential enquiry into maternal deaths and child health 2003–5. London: RCOG Press 2007.

Doll D, Ringenberg Q, Yarbro J. Antineoplastic agents and pregnancy. Semin Oncol 1989;16:337–45. Patient resources

www.cancer.gov/

health.yahoo.com/breastcancer-treatment/breast-cancer-and-pregnancy-treatment-patient-information-nci-pdq/healthwise–ncicdr0000062970.html

www.cancer.org/docroot/CRI/content/CRI_2_6x_Pregnancy_and_Breast_Cancer.asp

www.siteman.wustl.edu/PDQ.aspx?id=664&xml=CDR257535.xml

www.cooperhealth.org/content/pregnancyandcancer.htm

Fibroids in pregnancy Definition

These are uterine leiomyomata recognized during pregnancy. Epidemiology

• Fibroids are found in up to 40% of women before the age of 40.

• Fibroids are recognized in up to 4% of all pregnancies

• They are more common in:

• women over 40

• women of Afro-Caribbean origin

• pregnancy after assisted conception. Pathology

See Chapter 13.3, Fibroids. Fibroids do respond to oestrogen and may enlarge in pregnancy, although there are no consistent data to back this up. Aetiology

See Chapter 13.3, Fibroids. Clinical approach

History

• May have known fibroids

• The majority are asymptomatic and incidental scan findings

• Abdominal pain is the commonest symptom in pregnancy

• Previous myomectomy will need discussion regarding mode of delivery (see below).

Examination

• Usually not obvious on clinical assessment: scan only.

• May be ‘large for dates’.

• May be palpable on the uterus if large and/or multiple.

• Fetal malpresentation may rarely occur, e.g. breech, transverse, or oblique lie if lower segment or cervical fibroid.

• May be tender to palpate if in pain (usually discrete tenderness over fibroid).

Investigation

Abdominal ultrasound is usually the only investigation necessary. Transvaginal ultrasound is occasionally used to identify cervical fibroids. Magnetic resonance imaging is not usually necessary. Clinical features

The majority of pregnancies are unaffected by fibroids. The evidence on fibroids in pregnancy is controversial, as most of the published work is based on case–control studies that have significant confounding factors.

On balance there appears to be

• an association with subfertility (probably causal in 2–3% of cases, if submucosal, once other causes are excluded). Intramural and serosal fibroids do not appear to have a proven effect

• an association with miscarriage if submucoosal. Rates appear to be higher with fibroids versus no fibroids, but may be related to older age

• a small absolute increase in preterm delivery, malpresentation and Caesarean delivery

• a small increase in the rate of postpartum haemorrhage

• no convincing evidence for any causal relationship with

• increased perinatal morbidty or mortality

• placenta praevia/abruption or IUGR

• labour dystocia

• retained placenta or endometritis. Management

Subfertility and fibroids

Evidence for surgery for fibroids is of poor quality generally but overall appears to suggest

• some improvement in pregnancy rates

• best results seem to be with hysteroscopic resection for submucosal fibroids.

Miscarriage

Evidence for surgery for fibroids is of very poor quality and conflicting. Surgery to reduce the risk of further miscarriage for submucosal fibroids should only be performed on a case by case basis.

Antenatal care

Conservative

Reassurance that risks and complications are rare is usually all that is required. Routine monitoring of fibroid size or morphology is not necessary, nor is extra fetal growth monitoring. Antenatal care should be advised according to standard principles. There are no medical or surgical treatment options specifically for fibroids in pregnancy. In general ‘leave them alone!’

Special obstetric input will be required with

• significant fibroid pain

• abnormal fetal lie and where Caesarean section (CS) is required

• previous myomectomy.

Significant fibroid pain

This is the commonest clinical problem encountered with fibroids in pregnancy and is usually in the third trimester. Excessive fibroid growth, degeneration and necrosis due to ‘outgrowing its blood supply’ are often cited (and biologically plausible) but have no convincing evidence to support them. The pain’s aetiology is poorly understood. It may be mild and self limiting but more commonly is severe and requires hospital admission. Torsion of a pedunculated fibroid is very rare and no more common than in the non-pregnant population.

Management of fibroid pain

• Exclusion of other causes of abdominal pain is vital, especially

• placental abruption

• acute appendicitis/ovarian torsion

• UTI.

• The diagnosis is one of exclusion and is clinical.

• A mild pyrexia and vomiting may be present.

• A leucocytosis is not uncommon.

• Ultrasound will identify fibroids easily if unknown. Cystic changes are commonly seen but can also be seen within fibroids outside of pregnancy.

• Symptomatic treatment is required for pain relief. Commonly used agents are paracetamol and codeine derivatives. Buprenorphine, pethidine, and morphine may be required for severe pain.

• NSAIDs, although ideal, are generally avoided due to adverse effects on fetal renal and ductus function. They may be used off licence for a short time in refractory cases

• The majority of episodes are self-limiting (5–10 days)

• A few cases are prolonged and are very difficult to manage—pain team involvement may be helpful

• Surgery (myomectomy) for chronic unremitting pain has been described with successful results, but is not recommended due to concerns about uterine surgery during pregnancy (‘a last resort’).

• The pregnancy is unaffected.

Abnormal lie or presentation

• This is rare but occurs with significant lower segment/cervical fibroids

• TA and TV ultrasound with clinical assessment will help to show the relationship of presenting part and fibroid and exclude other causes, e.g. placenta praevia!

• A decision regarding the mode of delivery can be delayed until 37 weeks

• Elective CS at 39 weeks is the only safe mode of delivery if there is persistent obstruction.

Caesarean section with fibroids

• An experienced surgeon should be present.

• The ultrasound findings are a guide only and may not truly reflect the number and size of fibroids present— expect more than you think!

• Pfannensteil incision is generally preferred, but midline may be required if fibroids are large and/or multiple.

• There is a risk of upper segment incision being required if a fibroid is occupying the whole lower segment.

• The fibroid(s) should be avoided wherever possible and uterine incision kept clear of them as excess bleeding may occur.

• Difficulty delivering the baby may occur with multiple large fibroids—be prepared and have a plan B!

• Rarely myomectomy may be necessary at the same time to facilitate delivery or in the event of bleeding.

• Increased blood loss should be anticipated—cross-match blood.

• The absolute risk of hysterectomy is still very low and probably no more than for women without fibroids.

Previous myomectomy

• Previous myomectomy per se is not associated with any adverse pregnancy outcomes.

• Previous myomectomy in the non-pregnant state cannot be viewed the same as previous CS.

• Operative difficulty, especially bleeding and adhesions, should be anticipated if CS is required

• Evidence of poor quality suggests that;

• uterine rupture during pregnancy is negligible

• uterine rupture in labour is very low and successful vaginal delivery can be encouraged in the majority—labour should be managed empirically as for previous CS

• Uterine rupture may possibly be more common (very little convincing data)if

• the endometrial cavity was breached

• multiple uterine incisions were made

• more than one previous myomectomy.

Generally elective CS is recommended in these circumstances, although a trial of vaginal delivery is not unreasonable if a woman is fully informed

Postpartum care

Generally no specific extra care is required because of fibroids. The following can generally be advised:

• fibroid pain usually improves rapidly after delivery

• if fibroids have caused pain in one pregnancy they are more likely to do so in a future pregnancy

• obstructing fibroids will very likely do so again requiring repeat CS

• no fibroid monitoring is generally required unless they cause ongoing gynaecological symptoms

• future pregnancies are not likely to be significantly affected by fibroids. Further reading

Okolo S. Incidence, aetiology and epidemiology of uterine fibroids. In: Arulkumaran S (ed.) Best practice and research: clinical obstetrics and gynaecology, vol. 22: 4. Elsevier 2008: 557–88.

Khaund A, Lumsden MA. Impact of fibroids on reproductive function. In: Arulkumaran S (ed.) Best practice and research: clinical obstetrics and gynaecology, vol. 22: 4. Elsevier 2008: 749–60.

Klatsky PC, Tran NC, Caughey AB, et al. Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. Am J Obstet Gynecol 2008; 357–66.

Coronado GD, Marshall LM, Schwartz SM. Complications in pregnancy, labor, and delivery with uterine leiomyomas: a population-based study. Obstet Gynecol 2000;95:764–9.

Qidwai GI, Caughey AB, Jacoby AF. Obstetric outcomes in women with sonographically identified uterine leiomyomata. Obstet Gynecol 2006;107:376–82.

Manyonda I (eds). Uterine fibroids. In: Best practice and research: clinical obstetrics and gynaecology, vol. 22: 4. Elsevier 2008. Patient resources

www.nhsdirect.nhs.uk/articles/article.aspx?articleId=161

www.patient.co.uk/showdoc/23068738/

www.womenshealthlondon.org.uk/leaflets/fibroids/fibroidsresources.html

www.femalepatient.com/pdf/patob_0506.pdf

Obstetric cholestasis Definition

Obstetric cholestasis (OC), also called intrahepatic cholestasis of pregnancy, is a liver disease of pregnancy that affects approximately 1 in 200 pregnant women in the UK. It causes maternal pruritus in association with impaired liver function and raised serum bile acids and usually resolves within 12 weeks of delivery. Fetal complications include spontaneous preterm delivery, fetal anoxia, meconium-stained liquor, and intrauterine death. Epidemiology

The prevalence of OC varies in different ethnic groups, ranging from 0.% of Caucasians, to 1.5% of UK Asians, and up to 5% of native Chileans. The condition is more common in multiple pregnancy and in the winter months. Aetiology

OC has a complex aetiology with genetic, endocrine, and environmental components. Each will contribute to a different extent in individual women affected by OC. The aetiology of the fetal complications is likely to relate to the extent of the raised serum bile acids in the mother and fetus (Glantz et al. 2004).

Genetic factors

Evidence for a genetic aetiology comes from pedigree studies and mutation screens (Dixon et al. 2008). A small number of cases are caused by heterozygous mutations in biliary transport proteins (MDR3, BSEP, FIC1, MRP2) or the principal bile acid receptor (FXR). It is likely that genetic variation in the genes that encode these proteins, and others that influence bile homeostasis, also confers susceptibility to cholestasis in pregnancy.

Endocrine factors

Gestational rises in oestrogen and progesterone and their metabolites are likely to cause cholestasis in susceptible individuals (Reyes et al. 2008). A subgroup of women who had previously had OC develop symptoms of cholestasis when given oral contraceptives or in the latter half of the menstrual cycle. Also women with OC have higher levels of cholestatic oestrogen and progesterone metabolites in the serum and urine when pregnant. In vitro experiments have shown that these metabolites impair biliary excretion, thus implicating them in the aetiology of OC.

Environmental factors

OC is commoner in the winter months in Chile and Scandinavia. It occurs more frequently in women who are seropositive for hepatitis C and following ingestion of some antibiotics, e.g. co-amoxiclav or erythromycin (Geenes et al. 2009).

Aetiology of fetal complications

The largest study to date demonstrated that fetal complications (spontaneous preterm delivery, fetal anoxia and meconium-stained liquor) rarely occur if serial measurement of maternal fasting serum bile acids does not demonstrate levels >40 μmol/L. However, once the maternal bile acids rise to >40 μ mol/L the risk of pregnancy complications rises with each μmol/L increment above this level. Several additional studies have demonstrated a similar association between maternal serum bile acid levels and fetal risk.

In vitro studies have shown increased myometrial contractility in the presence of bile acids, and animal studies report increased rates of preterm delivery and meconium-stained amniotic fluid following infusion of bile acids. Administration of bile acids to in vitro cultured cardiomyocytes causes abnormal rhythm of contraction, leading to the hypothesis that raised fetal serum bile acids may result in a potentially fatal fetal arrhythmia.

Fetal autopsies are characterized by changes consistent with acute anoxia, and do not show evidence of chronic uteroplacental insufficiency. OC placentas have histological abnormalities consistent with hypoxic insults, and are consistent with the changes seen in placentas from a rodent model of OC. Meconium-stained amniotic fluid is reported in almost all OC-associated intrauterine deaths. The presence of meconium may also contribute to fetal anoxia. Prognosis

The maternal prognosis is usually good. It is important to exclude alternative underlying diagnoses. If none is present, the pruritus and hepatic impairment usually resolve 2 weeks after delivery. OC commonly recurs in subsequent pregnancies (Williamson et al. 2004). Affected women have an increased risk of gallstones, non-alcoholic cirrhosis and autoimmune hepatitis in later life (Ropponen et al. 2006). Clinical approach

Diagnosis

The diagnostic criteria used for OC vary in different studies. Ideally liver transaminases and serum bile acids should be measured. It is of value to measure serum bile acids as they have been shown to relate to fetal outcome (Glantz et al. 2004). Pruritus may precede biochemical abnormalities by several weeks (Kenyon et al. 2001) or alternatively the serum bile acids may be raised before symptoms are present, reflecting the aetiological heterogeneity of the condition. Therefore it is advisable to perform regular blood tests to assess the serum bile acid and transaminase level.

History

It is important to ensure there is no evidence of other liver diseases, e.g. infectious hepatitis, acute fatty liver of pregnancy, or pre-eclampsia with hepatic impairment. Otherwise, the history should ascertain the following:

• duration and location of pruritus. This classically occurs in the latter weeks of pregnancy, although the condition can present in the first trimester. The pruritus is most commonly perceived on the palms, soles and ‘all over’ the body and is not associated with a rash (apart from excoriations). However the localization of pruritus can be variable

• changes in the colour of urine/faeces

• family history

• multiple pregnancy or assisted conception

• risk factors for hepatitis C

• symptoms of cholecystitis

• cholestatic reactions to drugs in the past.

Examination

It is important to examine the skin for jaundice and to exclude a dermatological condition.

Investigations

OC is a diagnosis of exclusion. Pruritus and abnormal liver function can occur in women with a variety of other diagnoses, including diseases within the pre-eclampsia spectrum and infectious hepatitis. It can also be the presenting feature of biliary obstruction. It may also be complicated by postpartum haemorrhage secondary to malabsorption of vitamin K. Therefore, it is important to perform investigations to exclude these diagnoses/complications, including

• ultrasound of the liver and biliary tree

• hepatitis C serology

• clotting screen

• pre-eclampsia bloods. Management

General points

Once the diagnosis of OC has been confirmed the management strategy should include treatment of the maternal disease, fetal surveillance, and decisions about delivery. If there is a concurrent disease process, this should be treated.

Medical

• Ursodeoxycholic acid (UDCA) is the drug for which there is the most robust supporting data from clinical trials. It is a relatively hydrophilic bile acid that is found in small quantities in humans. It has been used successfully to treat cholestatic diseases outside pregnancy and is becoming increasingly popular as a treatment for OC. UDCA has several modes of action, including induction of bile acid excretion pathways, enhanced secretion of cholestatic oestrogen metabolites, and antiapoptotic effects. Most studies of the efficacy of UDCA in the treatment of OC have been small, although one included 130 cases randomized to receive UDCA, dexamethasone, or placebo (Glantz et al. 2005). UDCA has consistently been shown to improve maternal pruritus serum bile acids and transaminases (Geenes et al. 2009). However, no studies have been powered to establish whether it protects against the adverse fetal outcomes associated with OC.

• Aqueous cream with 2% menthol is a useful topical treatment that relieves pruritus. This is valuable for women who find the OC-associated itch extremely unpleasant, and it can help women get to sleep if they are suffering insomnia as a consequence of pruritus.

• Other drugs that have been used to treat OC include dexamethasone, S-adenosy methionine, cholestyramine, guar gum, and perioral activated charcoal. Although some small studies have reported maternal responses to these drugs none has consistently been shown to improve maternal symptoms and biochemical abnormalities.

• Vitamin K is often given with the aim of reducing the likelihood of postpartum haemorrhage, as this complication is thought to relate to vitamin K malabsorption secondary to steatorrhoea. There have been no clinical trials to evaluate whether this treatment is effective.

Maternal and fetal surveillance

• Once the diagnosis of OC has been established it is advisable to continue to monitor the maternal liver transaminases and serum bile acids. This will allow evaluation of the extent of the fetal risk (i.e. given the data relating fetal adverse events to maternal serum bile acid levels) and will ensure maternal wellbeing, given that pruritus and hepatic impairment may be the presenting features of other diseases, e.g. acute fatty liver of pregnancy.

• There is no evidence that regular fetal surveillance with cardiotochography facilitates the prediction of which OC pregnancies will be complicated by intrauterine death. However, this practice may reassure affected women and clinicians responsible for their care at the time it is performed.

• One study reported good fetal outcomes for OC pregnancies with a policy of routine amnioscopy at 36 weeks of gestation in addition to standard monitoring for fetal wellbeing (Roncaglia et al. 2002), but this approach may be more invasive than most obstetricians would choose.

Timing of delivery

• Some studies have reported good fetal outcomes with a policy of induction of labour at 38 weeks of gestation (Roncaglia et al. 2002). This policy has been adopted by a large proportion of clinicians in the UK as the fetal deaths appear to cluster after 37 weeks (Williamson et al. 2004). However, there have been no prospective studies to evaluate this practice.

• It is important to consider the risk of neonatal respiratory distress following delivery at 38 weeks of gestation, and to discuss the risks and benefits of this practice for the fetus/neonate with the mother. The neonatal risks of early delivery are considerably lower if the mother has undergone labour, and thus induction is likely to be associated with lower rates of respiratory distress than elective Caesarean section.

Postnatal care

Women whose LFTs remain abnormal 2 weeks after delivery should have further investigations and referral to a hepatologist.

The recurrence rate for OC is high. Women with a previous singleton pregnancy have a 70% chance of recurrent cholestasis in a subsequent pregnancy. The risk is lower following a multiple pregnancy.

Parous sisters and daughters of affected women have a 20-fold increased risk of developing OC.

Contraceptive advice

A subgroup of women who have had OC develop cholestasis following administration of ethinyl oestradiol or the combined oral contraceptive pill. Therefore, it is important to consider the risks of hormonal contraceptives. Ideally, affected women should use alternative forms of contraception, and if they use oral contraceptives they should have their liver function tests monitored. Further reading

Dixon PH, Williamson C. The molecular genetics of intrahepatic cholestasis of pregnancy. Obstet Med 2008;1:65–71.

Geenes VL, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol 2009;15:2049–66.

Glantz A, Marschall HU, Lammert F, Mattsson LA. Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid. Hepatology 2005;42:1399–405.

Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology 2004;40:467–74.

Kenyon AP, Piercy CN, Girling J, et al. Pruritus may precede abnormal liver function tests in pregnant women with obstetric cholestasis: a longitudinal analysis. Br J Obstet Gynaecol 2001; 108: 119.

MacKillop L, Williamson C. Diseases of the liver, biliary system and pancreas. In: Creasy, Resnik (eds) Maternal and fetal medicine, 6 edn. Elsevier 2008.

Nelson-Piercy C, Williamson C. Hepatic and gastrointestinal disorders. In: Greer I, Nelson-Piercy C, Walters B (eds) Maternal medicine, 1st edn. Elsevier 2007.

Reid R, Ivey KJ, Rencoret RH, Storey B. Fetal complications of obstetric cholestasis. BMJ 1976; 1: 87.

Reyes H. Sex hormones and bile acids in intrahepatic cholestasis of pregnancy. Hepatology 2008; 47: 37.

Roncaglia N, Arreghini A, Locatelli A, et al. Obstetric cholestasis: outcome with active management. Eur J Obstet Gynecol Reprod Biol 2002;100:167–70.

Ropponen A et al. Intrahepatic cholestasis of pregnancy as an indicator of liver and biliary diseases: a population-based study. Hepatology 2006; 43: 72.

Williamson C, Sund R, Riikonen S, et al. Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. Br J Obstet Gynaecol 2004;111:676–81. Internet resources

www.britishlivertrust.org.uk Patient resources

www.ocsupport.org.uk

Ovarian cysts in pregnancy Definition

Ovarian cysts diagnosed or known about during pregnancy. Epidemiology

Ovarian cysts are very common findings and their incidence is related to how commonly ultrasound is used throughout pregnancy. In early pregnancy attenders, rates of 5–10% are quoted for cysts >25 mm diameter. Cysts >5 cm are seen in approximately 1–2%. Pathology

All types of ovarian cyst have been described in pregnancy, but the most common are

• functional (presumably mainly corpus luteal) cysts (50–70%):may appear haemorrhagic

• dermoid cysts (10%)

• endometriomata (5–10%).

Malignancies are very rare and probably found in 10 cm

• the woman understands the risks of acute cyst accident (3–4%).

There is no consensus on ‘monitoring’ but it is reasonable to rescan in the second trimester if discovered in the first, and the third if discovered in the second. The majority of simple cysts (70–80%) will have resolved on rescanning. Persistent cysts (15–20%) can be rescanned 3 months postpartum. Large cysts are generally better removed electively postpartum.

Acute abdominal pain

This should be managed in the same way as outside pregnancy in the presence of a cyst. The clinical priorities are

• exclusion of ectopic pregnancy (and other causes of pain)

• resuscitation if haemodyanmically unstable due to haemorrhagic rupture

• accurate diagnosis on clinical and ultrasound parameters—haemorrhage and rupture are usually easy to diagnose and can generally be managed conservatively

• active intervention is needed when torsion is suspected.

Suspicious cysts and diagnostic difficulty

If cyst morphology is suspicious of possible malignancy or there is diagnostic difficulty.

• MRI may help to diagnose the likely aetiology.

• Cases should be referred to the cancer multidisciplinary team (MDT) or tertiary referral unit for decision-making.

• Great care in interpretation of tumour markers is required (as above).

• Ultimately cystectomy/oopherectomy/staging laparotomy may be required if significant concern exists: laparoscopic management is generally preferred if uterine size permits its use.

• The timing of surgery will depend upon the clinical concern, gestation, and maternal wishes: in advanced pregnancy this may be deferred till after delivery or performed at the time of Caesarean section.

• Evidence regarding safety of these procedures in pregnancy is generally very reassuring: the risks of miscarriage or preterm delivery are very small. Further reading

Valentin L. Imaging in gynaecology. In: Arulkumaran S (ed.) Best practice and research: clinical obstetrics and gynaecology, vol. 20: 6. Oxford: Elsevier 2006: 881–906.

Condous G, Khalid A, Okaro, et al. Should we be examining the ovaries in pregnancy? Prevalence and natural history of andexal pathology detected at first trimester sonography. Ultrasound Obstet Gynecol 2004;24:62–6.

Yazbek J, Salim R, Woelfer B, et al. The value of ultrasound visualization of the ovaries during the routine 11–14 weeks nuchal translucency scan. Eur J Obstet Gynecol Repro Biol 2007;132:154–8.

Zanetta G, Mariani E, Lissoni A, et al. A prospective study of the role of ultrasound in the management of adnexal masses in pregnancy. Br J Obstet Gynaecol 2003;110:578–83.

Postnatal depression

Approximately 1 in 10 women who deliver a baby will experience postnatal depression (Oates 2003). In a third of these women, the illness will last a year or more (Cox et al 1982), when it may have wide-reaching effects on the mother and her family if not identified and treated. Certain factors appear to increase the risk of developing postnatal depression including:

• young age of mother

• family/partner conflicts

• lack of social network

• substance misuse

• unwanted pregnancy or ambivalent to it

• pre-existing mental illness (anxiety or depression)

• frequent antenatal admissions

• family history of postnatal depression.

The management of postnatal depression includes a review of risks and benefits to mother and baby of various treatments. These will include the risks of mental illness to the mother, the baby, and other family; the potential risk benefit of treating the mother with certain medications that may affect the baby via breast milk, and fully informing and involving the woman in the decision-making process. The aim of referring to a psychiatrist is to determine whether any psychiatric symptoms are present and to discuss and advise the woman on management and coordinate between midwives, health visitors, social services, and the community mental health team to agree a suitable care plan during the postnatal period. Detection, screening, and prevention

Many mothers under-report their symptoms, either because they misattribute them to the normal consequences of childbirth, or because they feel guilty or embarrassed that they are feeling sad and miserable following the birth of their baby. For many women this is a confusing experience, as the social and cultural pressure to experience childbirth as a happy event is considerable. The diagnosis of postnatal depression can be a relief and a first step to recovery.

All women should be screened for depression at booking, during pregnancy, and at 1 and 3–4 months postpartum using the following two questions recommended by NICE (2007).

• During the past month, have you often been bothered by feeling down, depressed or hopeless?

• During the past month, have you often been bothered by having little interest or pleasure in doing things?

• A third question can be asked if the mother answers yes to either of these questions.

• Is this something you feel you need or want help with?

This should help to identify ‘at risk’ mothers early on. Specific screening questionnaires can also be used, such as the Edinburgh Postnatal Depression Scale (EPDS), although they are not essential to make a referral. They help identify illness severity, and response to treatment. Clinical features

• Low mood

• Tearfulness

• Irritability or anxiety

• Low energy or excessive tiredness

• Lack of ability to enjoy things (anhedonia)

• Biological symptoms, including poor sleep, loss of appetite, and weight loss

• Cognitive symptoms, including hopelessness, low self-esteem, guilt, suicidal ideation.

Postnatal depression can present with quite specific features centring on motherhood and the baby. These can include

• feelings of guilt and inadequacy as a mother

• lack of confidence in mothering ability

• anxieties about the baby’s health, sleeping or feeding, despite reassurance that the baby is well

• concern the baby is malformed or someone else’s

• excessive feelings of guilt about not feeling ‘maternal’ towards the baby

• reluctance to feed, hold, or cuddle the baby

• thoughts of suicide, self-harm, or harm to baby.

Some mothers experience difficulty bonding with their baby, and when this happens in the context of postnatal depression it may require attention in its own right. Long-term failures of attachment can have adverse consequences for the baby.

About half of all cases of postnatal depression are missed because family or healthcare professionals assume it is only ‘baby blues’ and will settle. These two conditions share the same clinical features but differences between the two are discussed below. Differences between baby blues and postnatal depression

Baby blues

• Onset around 3 days postpartum

• Incidence of up to 8 out of 10 mothers.

• Duration of 2–5 days: self-limiting.

Clinical features

• Anxiety, low mood, tearfulness, emotional lability, irritability, and confusion.

Aetiology

• Hormonal changes in oestrogen, progesterone, and prolactin are thought to be implicated because of the close temporal link between childbirth with the onset of baby blues. These affect central neurotransmission and are also associated with mood changes at other times of physiological change in premenstrual and perimenopausal women.

Treatment

• The majority of women who deliver a baby will experience baby blues. This is self-limiting and does not require any medication. It should settle spontaneously within a few days with support and reassurance from partner, family, and midwife.

• If symptoms persist after the first week after delivery and appear to be worsening, it is important to consider postnatal depression.

Postnatal depression

• Onset within 2–6 weeks postpartum

• Incidence of 1 in 10 mothers.

• Duration of weeks to months, and longer if untreated.

Aetiology

The aetiology of postnatal depression is multifactorial with physical, psychological, and social risk factors implicated.

Physical

There are possible links with obstetric factors, e.g. traumatic delivery, poor pain relief, sleep deprivation, being hospitalized

Psychological

• Family history of mental illness

• Past psychiatric history of depression unrelated to childbirth

• Previous postnatal depression (risk of recurrence is 1 in 4 in subsequent pregnancies)

• Personality factors, e.g. anxiety traits.

Social

• Poor relationship with partner

• No partner

• Poor parental relationships

• Loss of a parent at a young age

• Lack of social network, friends, extended family

• Financial or housing worries and uncertainties. History: key points

• Current presenting symptoms. Screen for affective symptoms (low or elated mood, tearfulness, low or increased energy, sleep disturbance, anhedonia, amotivation) and psychotic symptoms (auditory hallucinations, delusions, thought disorder).

• Screen for suicidal ideation and any thoughts of harming baby.

• Past psychiatric history: first contact with psychiatric services, any history of medications taken before or during pregnancy, any history of self-harm or suicide attempts, admissions to hospital with a mental health problem, particularly if under a section of the Mental Health Act (2007).

• Medication history. What medications is the patient currently taking? What medications have they been on prior to the pregnancy and when did these stop?

• Family history to identify any history of mental disorder

• Enquire about past or current substance misuse and alcohol use.

Examination: key points

• Ensure a thorough physical examination has been done to rule out physical causes for psychiatric symptoms.

• Perinatal psychiatry opinion to confirm diagnosis by detailed mental state examination.

• Appearance and behaviour: any evidence of poor eye contact and rapport, poor self-care?

• Speech: increased/reduced rate, rhythm, volume, content?

• Mood changes: how does the patient describe their mood?

• Thoughts: any self-harm or suicidal ideas, plans or intention? Any distressing guilty ideas or paranoid thoughts?

• Perceptions: any experiences of seeing or hearing things when alone that others cannot see, hear, or accept?

• Cognition: is concentration or memory impaired? Orientation to time, place, person?

• Insight: does the patient feel they are physically or mentally unwell? Do they wish to accept treatment and if required come into hospital?

Special investigations

• Exclude other possible causes of psychiatric symptoms such as a ‘hidden’ organic problem such as anaemia, gestational diabetes, thyroid disease or iatrogenic causes such as steroids.

• Consider blood tests to exclude physical conditions (FBC, WBC, U&E, LFTs, TFTs, glucose)

• Consider blood serum levels of medication to check if levels are therapeutic, e.g. lithium level. Treatment

Treatment may include psychological or biological interventions, and admission to a specialist Mother and Baby Unit may be necessary in severe cases where there is a high risk to mother or baby.

Psychological

In mild to moderate cases psychological support with guided self-help, supportive counselling or cognitive behaviour therapy (CBT) can be helpful. CBT involves a fixed number of sessions with a psychologist and structured work on the mother’s thoughts, actions, and feelings.

Biological

In more severe cases additional treatment with antidepressant medication is warranted. The specific choice of medication depends on whether the woman chooses to breastfeed and every effort should be encouraged for her to breastfeed if she wishes.

When choosing an antidepressant for a breastfeeding woman, NICE 2007 guidelines advise that

• tricyclics (TCAs) and the serotonin selective reuptake inhibitor (SSRI) sertraline are present in breast milk at relatively low levels.

• the SSRIs citalopram and fluoxetine are present in breast milk in relatively high levels

• all antidepressants carry the risk of withdrawal or toxicity in neonate. These are usually mild and self-limiting.

Although most medications can enter the breast milk in small quantities, antidepressant drugs with low excretion such as imipramine, nortryptiline, and sertraline may be preferred. Sertraline 50–200 mg po od is effective and well tolerated. The timing of this can be adjusted to avoid most of the drug entering the breast milk, e.g. the dose can be taken at night after the last evening feed and before the baby’s longest sleep.

With proper treatment under specialist supervision, postnatal depression usually resolves quickly and the woman is able to make a complete recovery. Most cases can be managed in the community with regular review.

However, in severe cases where there is a high risk, admission to a Mother and Baby unit is advisable to provide specialist care and preserve the attachment between mother and baby while she recovers. A mother may be more willing to accept voluntary admission to hospital if her baby can stay with her. If there is a high suicide risk or dangerous self-neglect (mother not eating or drinking) then electroconvulsive therapy (ECT) should be considered, as this can work quickly to relieve these life-threatening symptoms. If there is a high risk of harm to the mother or baby and she is unwilling to accept voluntary admission to hospital for treatment, she may need to be admitted under a section of the Mental Health Act (2007).

Untreated postnatal depression carries high morbidity and mortality, with suicide being a leading cause of maternal death in the UK (CEMACH 2007). The long-term inability of a mother to interact emotionally with her baby due to untreated depression can lead to abnormal cognitive and emotional development in the child (Nicholls et al 1999). Women who have had postnatal depression previously have a 1 in 4 chance of having a relapse after future deliveries and early referral to a perinatal psychiatrist and close monitoring is advised in the postnatal period after future deliveries. Further reading

Confidential Enquiry into Maternal and Child Health (CEMACH). Saving mothers lives: reviewing maternal deaths to make motherhood safer (2003–2007). London: CEMACH 2007.

Cox JL, Connor YM, et al. Prospective study of the psychiatric disorders of childbirth. Br J Psychiatry 1982;140:111–7.

Davies A, McIvor R, et al. Impact of childbirth on a series of schizophrenic mothers. Schizophrenia Res 1995;16:25–31.

NICE Clinical guideline 45. Antenatal and postnatal mental health National Institute of Clinical Excellence Feb 2007.

Nicholls KR, Cox JL. The provision of care for women with postnatal mental disorder in the UK: an overview. HK Med J 1999; 43–7.

Oates M. Perinatal psychiatric disorders: a leading cause of maternal morbidity and mortality. Br Med Bull 2003;67:219–29.

Oates M. Perinatal Maternal Mental Health Services. Royal College of Psychiatrists Council report CR88 April 2000. Patient resources

Support group: The Royal College of Psychiatrists website has a useful information leaflet: www.rcpsych.ac.uk/pnd

Mind: www.mind.org.uk and www.pni.org.uk.

The association for postnatal illness (APNI): www.apni.org

Meet-a-mum association (MAMA): www.mama.co.uk

Puerperal psychosis Presentation

Puerperal psychosis presents following 1 in 500 births. Onset is rapid and usually within a few days of delivery. The majority of cases are episodes of bipolar disorder triggered by childbirth in individuals who either have a history of bipolar disorder or an underlying vulnerability to bipolar disorder. Schizophrenia and psychotic depression can present as puerperal psychosis, although less commonly. Occasionally acute physical disorders such as infection or metabolic disturbances can also present with psychotic symptoms (hallucinations and delusions) and this possibility always needs to be considered.

Early symptoms of puerperal psychosis include sleep disturbance and confusion. These can be missed or mistaken for baby blues until more florid symptoms develop.

Mood disturbance is common and can include mania (elation, agitation, overarousal, overactivity, and or irritability) or depression, or a rapidly fluctuating combination of the two, a mixed affective state. About three-quarters of cases have a predominance of affective symptoms. Disorientation and perplexity are also relatively common. About one-quarter of cases will present with a more ‘schizophrenia-like’ picture with a predominance of psychotic symptoms. Delusional content will typically involve the patient’s baby, partner, family, or staff and may have a paranoid, grandiose, or religious flavour. Auditory hallucinations are relatively common, and when they are commanding in nature suggest high risk, especially when they involve commands to harm self or baby.

In the majority of cases, puerperal psychosis is severe and requires emergency psychiatric assessment and hospital admission. High levels of unpredictability and impulsivity in the context of a fluctuating mental state suggest high risk. Aetiology

A number of factors have been associated with an increased risk of developing puerperal psychosis following delivery:

• first birth

• previous psychiatric history (especially of bipolar disorder or puerperal psychosis)

• previous family history (especially bipolar disorder or puerperal psychosis in first-degree relative)

• single mother

• caesarean section

• previous or current perinatal death.

The close temporal relationship to delivery suggests a triggering effect of the rapid postpartum drop in pregnancy hormones, possibly by increasing dopamine sensitivity (Cookson 1982).

Women with a family history of bipolar disorder or puerperal psychosis have a higher risk of developing puerperal psychosis themselves. Women with a personal history of bipolar disorder have up to a 1 in 2 risk of a puerperal relapse if they do not receive appropriate treatment.

All women presenting for booking should be asked if they have any past or present mental health problems, any history of contact with a psychiatrist or specialist mental health team, or any family history of severe mental disorder, especially a family history of bipolar disorder or puerperal psychosis.

A thorough history and mental state examination is required, including an assessment of risk of suicide, self-harm, and harm to the baby. Clinical approach

History: key points

• Current presenting symptoms: screen for affective symptoms (low or elated mood, irritability or hostility, tearfulness, low or increased energy, sleep disturbance) and psychotic symptoms (auditory hallucinations, delusions, thought disorder).

• Past psychiatric history: ask about first contact with psychiatric services, any history of medications taken before or during pregnancy, any history of self harm or suicide attempts, admissions to hospital with a mental health problem, particularly if under a section of the Mental Health Act (2007).

• Medication history: what medication is the patient currently taking? What medications have they been on prior to the pregnancy, and when did these stop?

• Family history: look for evidence of psychiatric illness, particularly in first-degree relatives.

• Enquire about past or current substance misuse and alcohol use.

Examination: key points

• Ensure a thorough physical examination has been done to rule out physical causes for psychiatric symptoms.

• Refer for a perinatal psychiatry or liaison psychiatry opinion to confirm diagnosis by detailed mental state examination.

• Appearance and behaviour: any evidence of poor eye contact and rapport, poor self-care? Are they distractible, confused, or unable to respond appropriately to questions?

• Speech: increased/reduced rate, rhythm, volume, content? Are they speaking very fast (pressure of speech)

• Mood changes: how does the patient describe their mood? Do they seem elated or irritable? Is their mood labile?

• Thoughts: any self-harm or suicidal ideas, plans, or intention? Any distressing guilty ideas or delusional ideas with a paranoid, grandiose, or religious theme? Any changes to the form or flow of thought (e.g. flight of ideas)?

• Perceptions: any experiences of seeing or hearing things when alone that others cannot see, hear, or accept? Does the woman hear voices even if they are alone? What do the voices say? Do they command the woman to do things? Do they comment on the baby? Does the woman feel in control of her actions, feelings, and thoughts?

• Cognition: is there any impairment in concentration or memory? Orientation to time, place, person?

• Insight: does the patient feel they are physically or mentally unwell? Do they wish to accept treatment and if required come into hospital?

Special investigations

• Exclude other possible causes of psychiatric symptoms such as a ‘hidden’ organic problem such as anaemia, gestational diabetes, thyroid disease, or iatrogenic causes such as steroids.

• Consider blood tests to exclude organic conditions (FBC, WBC, U&E, LFTs, TFTs, glucose)

• Consider blood serum levels of medication to check if levels are therapeutic, e.g. lithium level.

• Consider if CT/MRI brain scan required to rule out organic pathology, e.g. brain tumour.

Treatment

This condition should be considered a psychiatric emergency due to the potential risk to the mother and baby. The associated suicide rate is in the order of 5% (Knops, 1993) and the infanticide rate is up to 4% (Altshuler et al., 1998).

The management of puerperal psychosis involves considering the risks of mental illness to the mother, the baby, and other family; the potential risk benefit of treating the mother with certain medications that may affect the baby via breast milk and fully informing and involving the woman in the decision-making process as far as possible while she is psychotic. The aim of referring to a perinatal psychiatrist is to determine the nature and degree of any psychiatric symptoms present and to discuss and advise the woman or team on the most appropriate management and coordinate between midwives, health visitors, social services, and the community mental health team to agree a suitable care plan during the postnatal period.

In those with symptoms, there is a 35 times increased risk of hospital admission for a psychotic illness within the first month of delivering a baby, (Kendell et al., 1987). In these cases, admission to a Mother and Baby unit is advisable to provide specialist care and preserve the bonding between mother and baby while she recovers. A mother may be more willing to accept voluntary admission to hospital if her baby can stay with her. If there is a high suicide risk or dangerous self-neglect (mother not eating or drinking) then electroconvulsive therapy (ECT) should be considered as this can work quickly to relieve these life-threatening symptoms. If there is a high risk of harm to the mother or baby and she is unwilling to accept voluntary admission to hospital for treatment, she may need to be admitted under a Section of the Mental Health Act (2007).

Antipsychotic or mood stabilizing medications can be used to relieve symptoms such as hallucinations, delusions, and affective disturbance. The choice of medication will depend upon individual patient circumstances and advice should be sought from a psychiatrist with special expertise in treating perinatal mental disorders. Agitation can be relieved using a short-acting low-dose benzodiazepine such as lorazepam 1–2 mg po as required. When prescribing a drug consider (NICE 2007)

• monotherapy over combination treatment

• treatment options that can allow the women to breast-feed if she wishes and is well enough to do so. Prognosis

With treatment the majority of mothers make a good recovery and return home within a few weeks.

However, there is around a 1 in 2 chance of having a relapse after subsequent deliveries. The 10-year recurrence rate is up to 80% (Garfield et al., 2004).

A significant proportion of women who experience puerperal psychosis will also go on to develop bipolar affective disorder later in life (1 in 4). References

Altshuler LL, Hendrick V, Cohen LS. Course of mood and anxiety disorders during pregnancy and the postpartum period. J Clin Psych 1998; 59 (Supp 2): 29–33.

Confidential Enquiry into Maternal and Child Health (CEMACH). Saving mothers lives: reviewing maternal deaths to make motherhood safer (2003–2007). Dec 2007.

Cookson JC. Post-partum mania, dopamine and oestrogens. Lancet 1982; ii: 672.

Cox JL. Connor YM, Kendell RE. Prospective study of the psychiatric disorders of childbirth. Br J Psychiatry 1982;140:111–7.

Davies A, McIvor R, Kumor RC. Impact of childbirth on a series of schizophrenic mothers. Schizophrenia Res 1995;16:25–31.

Garfield P, Kent A, Paykel ES, et al. Outcome of postpartum disorders: a 10 year follow-up of hospital admissions. Acta Psychiatr Scand 2004;109:434–9.

Kendell RE, Chalmers JC, Platz C. Epidemiology of puerperal psychoses. Br J Psychiatry 1987;150:662–73.

Knops GG. Postpartum mood disorders. A startling contrast to the joy of birth. Postgrad Med 1993; 103–4.

NICE Clinical guideline 45. Antenatal and postnatal mental health National Institute of Clinical Excellence Feb 2007.

Nicholls KR. Cox JL. The provision of care for women with postnatal mental disorder in the UK: an overview. HK Med J 1999; 43–7.

Oates M. Perinatal psychiatric disorders: a leading cause of maternal morbidity and mortality. Br Med Bull 2003;67:219–29.

Oates M. Perinatal Maternal Mental Health Services. Royal College of Psychiatrists Council report CR88 April 2000. Patient resources

The Royal College of Psychiatrists: www.rcpsych.ac.uk/pnd

Mind: www.mind.org.uk and www.pni.org.uk.

Pre-eclampsia and eclampsia Definitions

Pre-eclampsia is a multisystem disease of pregnancy defined clinically by pregnancy-induced hypertension (blood pressure (BP) of >140/90 mmHg on two occasions 4 hours apart, or one reading of >170/110 mmHg) and proteinuria (>0.3 g/24 hours) after 20 weeks’ gestation.

Severe pre-eclampsia occurs with BP ≥170/110 on two occasions along with significant proteinuria (>1 g in 24 hours). Clinical features of severe pre-eclampsia may be apparent at BP worldwide. The incidence of the disease varies according to the population studied and rates in Latin America are much higher. In developed countries it is perinatal rather than maternal mortality that is frequently the problem, and PE is the commonest cause of iatrogenic prematurity. In addition, it frequently coexists with fetal growth restriction (FGR) and placental abruption, other important causes of adverse perinatal outcome.

HELLP affects 20% of pregnancies complicated with severe pre-eclampsia (with 15% presenting in second trimester, 50% in the third trimester, and 35% postpartum).

Eclampsia complicates ~1 in 2000 pregnancies (1–2% of pre-eclampsia cases) with one-third occurring postpartum, the highest risk being the first 24–48 hours; 3% of cases will also develop HELLP. Pathology

The aetiology of pre-eclampsia is unknown.

In early pregnancy the extravillious trophoblast invades the uterine spiral arteries transforming them from thick-walled muscular vessels to wider diameter thin-walled vessels of low resistance. This process is complete by 20–24 weeks. In women with pre-eclampsia there is failure of normal trophoblastic invasion of the myometrial spiral arteries causing them to maintain their thick wall and high resistance.

This reduction in uteroplacental perfusion and relative placental hypoxia leads to oxidative stress and there is release of antiangiogenic and other factors into the maternal circulation. The resultant vasoconstriction causes hypertension and endothelial damage leading to loss of protein from the intravascular space. This mechanism forms the common basis of the developing maternal syndrome affecting multiple systems including renal, hepatic, haematological, and cerebrovascular. Aetiology

There is an increased chance of developing pre-eclampsia in cases of

• primigravidity

• multigravidity with a long interpregnancy interval or new partner

• previous history of pre-eclampsia

• extremes of age

• family history (increased incidence if mother and sisters affected)

• ethnic origin (more common among Africans)

• increased body mass index

• essential hypertension

• Pre-existing renal disease, diabetes mellitus, or systemic lupus erythematosus

• antiphospholipid syndrome and inherited thrombophilia

• abnormal uterine artery Doppler flow at midgestation. Prognosis

Pre-eclampsia is the second most common cause of maternal deaths. In the UK, 18 women died from severe pre-eclampsia and its complications in the 2003–5 Confidential Enquiry. The commonest cause of substandard care is failure of antihypertensive therapy.

With HELLP, maternal mortality is 1%. Serious complications include renal failure, abruption, DIC, and pulmonary oedema. Fetal mortality rates range from 7.7% to 60%, depending on gestation at birth.

With eclampsia, maternal mortality is 1%. Serious complications include acute renal failure, which is reversible (4%), DIC (3%), aspiration/RDS (3%), intracranial haemorrhage/transient blindness, and fetal bradycardia. Clinical approach

Diagnosis

History

Presentation can range from asymptomatic, raised BP, and proteinuria detected on routine antenatal screening, to a combination of symptoms and signs of varying severity, including

• headache, visual disturbance, epigastric and/or right upper quadrant pain

• worsening peripheral and periorbital oedema

• nausea and vomiting,

• feeling generally unwell with flu-like symptoms

• reduced fetal movements

• abdominal pain and bleeding (due to an abruption)

• evidence of cerebrovascular accidents.

In HELLP syndrome symptoms most commonly reported are epigastric pain and right upper quadrant tenderness (65%). In addition, haematuria may be reported.

In eclampsia there is a history of seizures (in the absence of known epilepsy) and postictal confusion.

Examination

BP should be checked more than once. Oedema is not necessary for the diagnosis of pre-eclampsia, but worsening facial or sacral oedema persisting after rest is significant. Mothers with pre-eclampsia may be small for dates on routine clinical palpation.

In case of severe PET there may be epigastric and right upper quadrant tenderness. Tenderness over the liver and jaundice may be signs of HELLP. Look for evidence of disseminated intravascular coagulation. Chest examination and pulse oximetry may reveal signs of pulmonary oedema. Clonus ≥3 beats is associated with cerebral irritation, and fundoscopy may reveal papilloedema. Although checking the deep tendon reflexes has become a part of the routine clinical examination of pre-eclamptic women, the predictive value of brisk reflexes is uncertain.

With eclampsia, grand mal generalized clonic seizures will be present. It is worth noting that 20% of women are normotensive at presentation.

Investigations

Urine tests

• Urinalysis indicating ≥ +2 protein on urine dipstick is significant and quantitative measurement should follow.

• Send an MSU to rule out infection as the cause of proteinuria.

• A 24-hour urine collection for protein is the ‘gold standard’ quantitative measurement for proteinuria.

• Protein–creatinine ratio can be performed on a single urine sample.

Blood tests

• FBC: raised haemoglobin and haematocrit due to haemoconcentration or a low haemoglobin due to haemolysis. Platelets may also be low.

• Urea and electrolyte analysis may reveal raised urea and creatinine.

• Liver function tests may show raised transaminases. AST levels greater than 2000 IU/L are associated with disordered mental state, jaundice, and extreme hypertension.

• Urate levels normally equate to gestation (i.e. new-onset pre-eclampsia, those who are symptomatic, have significant hypertension (≥140/90) with ≥2 + protein on urinalysis, haematological/biochemical disturbance or fetal effects should be admitted for further assessment. Initial monitoring should include

• 4-hourly BP measurements (including mean arterial pressure calculation)

• cardiotocography (CTG) twice a day

• 24-hour urine collection for protein

• TED stockings

• daily urinalysis

• ultrasound for fetal size, liquor volume, and umbilical artery Doppler.

The primary major failing in clinical care resulting in death is inadequate treatment of BP with subsequent intracranial haemorrhage. Second, but equally important, is iatrogenic fluid overload and pulmonary oedema.

Specific treatments

Antihypertensives

Antihypertensives control BP but do not stop the disease process of pre-eclampsia. All antihypertensives reduce the risk of severe hypertension in women with mild–moderate pre-eclampsia; however, there is insufficient evidence whether there is a reduction in serious outcomes.

Treatment of hypertension should be considered when diastolic BP measurements are persistently above 105 mmHg or systolic BP is >160 mmHg. Before 28 weeks, consider starting treatment when diastolic BP is >90 mmHg.

Bed rest may be associated with reduced risk of severe hypertension and preterm birth but there is insufficient evidence to advise this.

The main concern with antihypertensive therapy is of reduced placental perfusion and consequent FGR. Sudden drops in BP should be avoided and the aim is to keep the BP >130/80 mmHg. Women on antihypertensives should have serial growth scans to detect FGR.

Angiotensin-converting enzyme (ACE) inhibitors are contraindicated because of fetal effects (oligohydramnios, renal failure, and hypotension). Diuretics should only be used for treatment of pulmonary oedema as they deplete the intravascular volume.

There is no difference in choice of drug.

• Methyldopa: α-agonist with centrally mediated effect inhibiting vasoconstriction has a long half-life and slow onset of action. It is a safe drug supported by many years of experience. There is no evidence of long-term adverse effects in exposed fetuses. The main adverse effects are maternal drowsiness (with the sedative effect usually resolving after a week) and depression. Administration must be avoided with deranged LFTs. Treatment is initiated with a loading dose, 500–750 mg orally, followed by a maintenance dose between 250 mg bd to 1 g tds.

• Nifedipine: calcium channel blocker that inhibits influx of calcium ions in to vascular smooth muscle causing arterial vasodilatation. There is no evidence of harm to the fetus but safety data are limited compared with methyldopa. Side-effects include headache and facial flushing. Slow-release preparations should be used as standard release is more likely to cause a sudden drop in BP. The initial dose is slow-release 10 mg bd orally, which can be increased to 40 mg bd.

• Adrenoreceptor blockers: these act on the heart, peripheral blood vessels, airway, pancreas, and liver receptors. Labetalol is a combined alpha- and beta-blocker, which in addition to its cardiac effects it lowers peripheral resistance by causing arteriolar vasodilation. Past studies have highlighted the possibility of an increased risk of FGR in those treated with beta-blockers. Side-effects are few but must be avoided in asthmatics. Treatment is commenced with labetolol 100 mg bd orally, increasing to a maximum of 2.4 g per day in three or four divided doses. In management of severe hypertension, it can be administered i.v. as either a bolus or infusion.

• Hydralazine: a vasodilator with a direct relaxing effect on smooth muscle in the blood vessels, predominantly in the arterioles. Mainly used intravenously, as a bolus or infusion, in controlling severe hypertension prior to delivery. Side-effects include maternal tachycardia and further doses should be avoided with a maternal heart rate >120 bpm. Treatment is initiated with an i.v. bolus of 5 mg, which can be repeated every 15 minutes up to a total of 20 mg.

Thromboprophylaxis

While an inpatient, TED stockings should be worn.

Women with significant proteinuria are at an increased risk of thromboembolism and prophylactic low molecular weight heparin should be given.

Fetal monitoring

Maternal perception of fetal movements is a useful crude clinical guide of wellbeing.

In women with pre-eclampsia fortnightly growth US scans should be performed, as pre-eclampsia presenting prior to 36 weeks is associated with a high risk of reduced fetal growth and neonatal morbidity and mortality. If there are concerns, umbilical artery Doppler studies are arranged in the intervening week (see Chapter 7.19, IUGR)

Steroids

If delivery before 34 weeks is anticipated then consider steroids for fetal lung maturity.

Magnesium sulphate

Used in severe pre-eclampsia or eclampsia when delivery has been decided on. It is administered for 24 hours after the last seizure or delivery, whichever is latest. The MAGPIE study demonstrated that, used prophylactically, MgSO₄ reduces the risk of convulsions and of abruption regardless of the severity of pre-eclampsia. Side-effects and toxicity include flushing, blurred vision, slurred speech, weakness, somnolence, loss of patellar reflexes, decreased urine output, respiratory and cardiac arrest. If any of these occur or if there are recurrent convulsions, serum levels should be checked.

Treatment of toxicity involves stopping the infusion and administering Ca²⁺ gluconate i.v., 1 g over 3–10 minutes.

Delivery

The decision to deliver includes maternal and fetal aspects of wellbeing. The threshold falls with gestation.

In women who are at or near term, the decision to deliver is easier. In women who are 160/110 and/or mean arterial pressure (MAP) >125. With MAPs >145 there is loss of cerebral autoregulation with risk of cerebral haemorrhage. BP can drop suddenly with intravenous treatments and cause fetal bradycardia. Therefore, preloading with colloid (up to 500 mL) and continuous fetal monitoring is necessary with parenteral antihypertensives. Hydralazine (i.v. bolus or infusion), labetolol (i.v. bolus or infusion), or nifedipine (orally) are used for the acute management of hypertension. The aim is to maintain a BP of 140–150/80–90 mmHg. It should be checked every 15 minutes until it is stabilized, then every 30 minutes.

Owing to the risks of fluid overload and pulmonary oedema, input should be restricted to 85 mL/hour including all infusions (oxytocin, antihypertensives, magnesium sulphate). Output needs to be monitored and in the acute situation a catheter with hourly urometer should be used. Oliguria is often seen with severe pre-eclampsia and is defined as a urine output of less than 100 mL/4 hour. Renal failure rarely complicates pre-eclampsia and in most cases diuresis occurs postpartum.

An initial 500-mL bolus of colloid can be given if necessary. However, further fluid replacement may need to be guided by invasive monitoring (central venous pressure (CVP) line), particularly in the presence of acute blood loss.

Continuous pulse oximetry will help to detect early pulmonary oedema.

In women who are at risk of seizures, particularly with CNS symptoms (severe headache, agitation, clonus), MgSO₄ should be administered. O ₂ saturation, respiratory rate, urine output, and deep tendon reflexes should be checked hourly to monitor for toxicity.

Once BP is controlled in women with severe pre-eclampsia, delivery needs to be considered. Individual circumstances will dictate whether delivery can be delayed for the administration of steroids in preterm gestations. Conservative management at very early gestations may improve neonatal outcome but this needs to be balanced against maternal wellbeing. The mode of delivery will depend on gestation, maternal and fetal wellbeing. If 34 weeks, the chance of a vaginal delivery is up to 65%.

Syntocinon should be given for the third stage. Products containing ergometrine should be avoided due to the risk of further hypertension.

HELLP syndrome

The management of HELLP syndrome follows that of severe pre-eclampsia focusing on the correction of coagulation disorders and platelet levels. Involving a haematologist early is essential. Platelet transfusion is considered when the platelet count is were small and the reassurance about safety of aspirin in pregnancy applies mainly to lower doses. Further reading

Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2001; 2: CD002252.

Altman D, Carroli G, Duley L, et al. Magpie Trial Collaboration Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet. 2002;359:1877–90.

Askie LM, Duley L, Henderson-Smart DJ, Stewart LA; PARIS Collaborative Group. Antiplatelet agents for prevention of preeclampsia: a meta-analysis of individual patient data. Lancet 2007;369:1791–8.

Catanzarite VA, Steinberg SM, Mosley CA, et al. Severe preeclampsia with fulminant and extreme elevation of aspartate aminotransferase and lactate dehydrogenase levels: high risk for maternal death. Am J Perinatol 1995;12:310–3.

Davison J, Baylis C. Renal disease. In: de Swiet M (ed) Medical disorders in obstetric practice, 3rd edn. Oxford: Blackwell Science 1995: 226–305.

Duley L, Henderson-Smart DJ, Knight M, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2004; 1: CD004659.

Girling JC, Dow E, Smith JH. Liver function tests in pre-eclampsia: importance of comparison with a reference range derived for normal pregnancy. Br J Obstet Gynaecol 1997;104:246–50.

Magee LA, Duley L. Oral beta-blockers for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2003; 3: CD002863.

Matchaba P, Moodley J. Corticosteroids for HELLP syndrome in pregnancy. Cochrane Database Syst Rev 2004;: CD002076.

Meher S, Duley L. Rest during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure. Cochrane Database Syst Rev 2006; 2: CD005939.

PRECOG Evidence used to develop the PRECOG guidelinePRECOG Evidence used to develop the PRECOG guideline. Action on pre-eclampsia. www.apec.org.uk 2004b.

RCOG Green Top Guidelines. Antenatal Corticosteroids to Prevent Respiratory Distress Syndrome. Guideline No. 7. London, RCOG Press, 2004. www.rcog.org.uk

RCOG Green Top Guidelines. The management of severe pre-eclampsia/eclampsia. Guideline No. 10A. London, RCOG Press 2006: www.rcog.org.uk

Royal College of Gynaecologists and Obstetricians. Why mothers die 2003–2005, 7th report. London: RCOG Press www.cemach. org.uk

Rumbold AR, Crowther CA, Haslam RR, et al. ACTS Study Group. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med 2006;354:1796–806.

Sarris I, Bewley S, Agnihotry S (eds). Training in obstetrics and gynaecology. Oxford: Oxford University Press 2009.

Scottish obstetric guidelines and audit project. The management of mild non-proteinuric hypertension in pregnancy. Guideline update, March 2002.

Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365:785–99.

Sullivan CA, Magann EF, Perry KG Jr, et al. The recurrence risk of the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) in subsequent gestations. Am J Obstet Gynecol 1994;171:940–3.

Wilson BJ, Watson MS, Prescott GJ, et al. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. BMJ 2003; 326: 845.

Yamasmit W, Chaithongwongwatthana S, Charoenvidhya D, et al. Random urinary protein-to-creatinine ratio for prediction of significant proteinuria in women with preeclampsia. J Matern Fetal Neonatal Med 2004;16:275–9. Internet resources

www.rcog.org.uk

www.cemach.org.uk

www.apec.org.uk Patient resources

www.patient.co.uk/showdoc/23069028/

www.rcog.org.uk/womens-health/clinical-guidance/pre-eclampsia-what-you-need-know

www.pre-eclampsia.co.uk

www.preeclampsia.org

www.pre-eclampsia-society.org.uk

Premalignant conditions of the genital tract in pregnancy Definition

Cervical intraepithelial neoplasia (CIN) diagnosed or already known about during pregnancy. Epidemiology

CIN is relatively common in young women and is present in 1–4% of pregnancies. It is no more common than in the non-pregnant state. Pathology

The pathology due to HPV acquisition is no different to the non-pregnant state (see Chapter 14.3, Cervical dysplasia and human papillomavirus). Aetiology

See Chapter 14.3, Cervical dysplasia and human papilloma-virus. Pregnancy does not alter the natural history of CIN, despite large changes to the cervix Clinical approach

History

• May have known CIN

• Asymptomatic and incidental smear finding in the vast majority

• In cases of vaginal bleeding that is not due to CIN as it is a preclinical disorder, look for other causes.

Examination

• CIN is not visible on routine speculum examination and requires colposcopy ±cervical biopsy as for non-pregnancy

• Cervical changes due to pregnancy need to be borne in mind when assessing the cervix at colposcopy:

• large transformation zone and ectropion

• cervical oedema

• increased and thickened cervical mucous.

Investigation

Abnormal smears should be referred for colposcopy as when not pregnant. Generally, cervical biopsy is unnecessary. Clinical features

Pregnancies are unaffected by CIN and vice versa. Women can be reassured that there is no association with obstetric complications.

Management

Should smears be taken in pregnancy? There is general agreement that

• cervical smears are not taken routinely as part of pregnancy care

• if the pregnancy coincides with their 3-year interval smear and the smear history is normal then preference is for a postnatal smear at 3 months

• if they are significantly over their 3-year interval, a smear should be taken in the second trimester

• if there has been an abnormal smear prior to pregnancy and the smear is due, a smear should be taken in the second trimester.

Abnormal smears

Abnormal smears should always be referred for colposcopy as when not pregnant. The aims of colposcopy in pregnancy are

• colposcopic exclusion of invasive disease

• delay of biopsy or LLETZ (large loop excision of transformation zone) till after delivery.

The rate of cervical cancer in pregnancy is very low and data from retrospective cohort studies support the safety of delay in treatment once invasion is excluded.

• If ≤CIN 1, repeat colposcopy 3 months postpartum.

• If CIN 2/3, repeat colposcopy in third trimester or 3 months postpartum if already in late pregnancy.

• Follow-up postpartum is very important as regression during pregnancy is unlikely.

When should a biopsy be taken?

If invasion is suspected then a diagnostic biopsy is necessary. Choice of biopsy (punch/loop/wedge) is arbitrary but haemorrhage should be anticipated (up to 25%) and managed accordingly.

LLETZ should be considered non-therapeutic as rates of residual disease are very high (at least 50%), i.e. diagnostic only.

Follow-up is therefore essential in all pregnant women with abnormal cytology.

Cervical glandular intraepithelial neoplasia

The management of cervical glandular intraepithelial neoplasia (CGIN) is controversial and difficult even outside of pregnancy. Again abnormal glandular cells should be referred for colposcopy with the aim of excluding invasive disease and delaying biopsy or treatment till 3 months postnatal. Other premalignant conditions

Vaginal, vulval, and peri-anal intraepithelial neoplasia (VAIN, VIN, and PAIN) are all very rare in pregnancy and should be managed as outside of pregnancy. They are unaffected by pregnancy and vice versa. Excision or definitive treatment can invariably be left till after delivery unless invasive disease is suspected. Further reading

Douvier S, Filipuzzi L, Sogot P. Management of cervical intra-epithelial neoplasm during pregnancy. Gynecol Obstet Fertil 2003: 31: 851–5.

NHSCSP publication no 20. April 2004. Colposcopy and Programme Management. Guidelines for the NHS Cervical Screening Programme.

Selleret L, Mathevet P. Precancerous lesions during pregnancy: diagnostic and treatment. J Gynaecol Obstet Biol Repro 2008: 37 (Suppl 1): S131–8.

Preterm labour Definition

Preterm delivery (PTD) is the birth of a viable fetus before 37 completed weeks (or 259 days) of gestation. Spontaneous preterm labour is the precursor of one-third of all PTD. A further third of preterm births follow pre-term prelabour rupture of membranes and the rest are medically indicated. Epidemiology and importance

The worldwide incidence of PTD ranges between 5% and 13%. In the developed economies there is evidence of an increasing trend of PTD during the last decade, attributed to higher order pregnancies resulting from assisted conception techniques. A further contributor is the greater willingness of modern obstetricians to ‘rescue/salvage’ fetuses at earlier gestations. There is a marked racial disparity in the incidence of preterm delivery. In the USA, 8.8% of White and 18.9% of Black births occur before 37 completed weeks.

Preterm births account for more than 75% of perinatal mortality in normally formed babies. Infants who survive preterm delivery are at increased risk of subsequent neurodevelopmental deficits and lung disease. Advances in neonatal intensive care have led to an increase in the number of infants that survive PTD. For example, of the 10 241 white singleton babies born weighing less than 1000 g (22–28 weeks of gestation) in the USA during 1960, only 67 (0.65%) survived. Today, babies in this category can expect at least an 80-fold higher rate of survival. Only a reduction in the rate of PTD can be expected to translate to a significant reduction in perinatal mortality and morbidity and in the cost of neonatal care. Unfortunately, modern obstetric care continues to fail on this front because the major contributing pathological processes remain unrecognized and/or untreated, in spite of advances in diagnostics and therapeutics. Without a greater understanding of these underlying factors, there is very little chance of progress towards the prevention of PTD.

The cost of acute hospital care for preterm infants in the UK is approximately £35 000 per infant. Among neonates born ≤28 completed weeks of gestation, this is estimated to be £500 000. In the USA, the current annual cost of care of premature babies by March of Dimes is $26.2 billion. After discharge from hospital, the healthcare and social services continue to incur substantial costs for their special needs, education, and long-term disability. These cost estimates exclude the hidden costs of disruption to family life, emotional and psychological stress, childcare costs for existing children, transportation to and from the hospital, and loss of earnings on the part of the parents. For infants weighing less than 900 g, cost–benefit analyses studies indicate that the total costs per survivor are in excess of the total average lifetime earnings per survivor. Clinical assessment

The clinical diagnosis of preterm labour is unreliable. A policy of intervention with the onset of uterine activity prior to changes in the cervix exposes many women to unnecessary and potentially harmful treatment. On the other hand, withholding treatment until clinical evidence of cervical change may result in late institution of essential treatment. At present there are no sensitive and specific tests capable of predicting preterm labour and none of the currently available interventions, including tocolysis, antibiotic therapy, bed rest, and cervical cerclage, has been shown conclusively to prevent PTD and improve perinatal outcome. These approaches are reactive and ineffective against a process that is driven by a cascade mechanism.

A detailed and comprehensive history is a useful adjunct to the assessment of the risk of PTD. Prior history of spontaneous PTD or second trimester miscarriage suggests a significantly increased risk of recurrence. The magnitude of this risk is directly related to the number of prior PTD or late miscarriage, and the outcome of the immediate preceding pregnancy (Table 9.12.1). Prior history is, however, of no value in women in their first pregnancy. Other factors include history of cervical surgery for CIN disease, late terminations of pregnancy, collagen diseases, lupus anticoagulant, current multifetal gestation, stressful life-style/occupation, use of recreational drugs, and history of urinary tract infections. Yet, over 50% of women with PTD display no identifiable clinical risk factors. Evidence has now accumulated that at least 70% of ‘idiopathic spontaneous preterm labour’ is attributable to subclinical genital tract infections, mostly atypical micro-organisms such as Mycoplasma hominis, Ureaplasma urealyticum, anaerobic species, and a host of other subpathogenic organisms associated with bacterial vaginosis. These organisms are nonpyrogenic and not easily detected on conventional microbiological techniques. Clinical assessments including bedside tests and microbiological investigations may therefore be falsely reassuring and misleading.

There may be uterine activity or irritability, sometimes only evident on the tocometer. The maternal heart should be auscultated to exclude obvious cardiac murmurs. These women are candidate recipients of combinations of corticosteroid and vasoactive tocolytic agents with a risk of cardiac failure and pulmonary oedema. The presence of pyrexia, uterine irritability, or tenderness associated with leucocytosis or fetomaternal tachycardia suggests clinical chorioamnionitis. There may be offensive vaginal discharge. Clinical chorioamnionitis is, however, present in only 12% of women with proven intra-amniotic infection. Vaginal examination is essential to exclude rupture of fetal membranes, assess the state of the cervix, obtain cervicovaginal samples for sexually transmitted pathogens and group B Streptococcus (GBS). For optimal detection of GBS colonization, samples should be obtained from the lower third of the vagina, incorporating a perineal sweep and rectal or peri-anal samples. This is then placed in a transport medium and transported rapidly to the laboratory for plating. Failure to follow these steps results in failure to detect as much as 65% of cases of GBS colonization. Bedsides urine tests for protein, leucocytes and nitrites should be performed and antibiotic therapy commenced if there is suspicion of urinary tract infection. This should take cognisance of the most likely pathogen in the local population and subsequently reviewed with sensitivity results.

About one-third of the cervix is supravaginal and inaccessible to the examining fingers. Furthermore, the process of cervical effacement and dilatation starts at the internal os and may not be observed by speculum-assisted visualization of the cervix or digital palpation. If the facilities and expertise are available, transvaginal sonographic examination of the cervix may help to refine the risk of progression to PTD. An inverse correlation exists between cervical length and the risk of PTD. Between 24 and 28 weeks’ gestation, cervical length less than 2.5 cm is associated with a 6–10-fold increase in the risk of PTD. Fetal presentation should be confirmed also, as the accuracy of clinical determination decreases with early gestational age. Estimation of fetal weight and amniotic fluid can be made. Application of Doppler waveform analysis may assist in distinguishing the growth-restricted preterm fetus from its appropriately grown counterpart. Occasionally, an unsuspected abruption or fetal anomaly may be diagnosed.

Table 9.12.1 Risk of preterm delivery based on prior pregnancy outcome (Hoffman 1995)

Principles of management

Optimal neonatal services

The availability of specialist personnel, equipped for and skilled in advanced neonatal resuscitation with round the clock capability for ventilation of the very premature infant and back up laboratory services, is essential in ensuring good neonatal outcome. Neonatal survival rates including intact survival are much higher in such centres than in relatively less well equipped and staffed units. Unfortunately, this level of care is neither available nor sustainable in all obstetric units. The current practice of transferring women at risk of PTD to regional units involves relocation of mother and baby to centres far away from home with further disruption to family life. There are knock-on implications also for the training of resident obstetricians working in the transferring hospitals.

Corticosteroids

Antenatal maternal steroid injection at ≤32 weeks gestation is associated with a 60% reduction in the risk of respiratory distress syndrome, 30–40% reduction in the risk of major intraventricular haemorrhage and necrotizing enterocolitis. These beneficial effects act synergistically to produce an overall reduction in perinatal morbidity and mortality. The corticosteroid of choice supported by published evidence is betamethasone 12 mg given intramuscularly in two doses, 24 hours apart. Weekly antenatal steroid administration to maintain these beneficial effects should be discouraged, as there are no data at present to support its use in this way. Moreover, evidence from experimental animal studies document a host of harmful effects associated with weekly steroid administration, including altered central nervous system development, impaired growth/low birthweight, necrotizing enterocolitis, placental abnormalities, adrenal suppression, and precipitation of maternal diabetes.

Tocolysis

Tocolysis as a sole intervention does not improve neonatal outcome nor significantly delay preterm birth. On the other hand, it may be associated with significant fetomaternal morbidity and mortality. It is therefore reasonable not to use tocolysis if the risks are judged to outweigh the benefits. The current accepted indications for the use of tocolysis include delaying delivery for 24–48 hours to initiate or complete corticosteroid administration, or for administered steroids to take effect, controlling uterine activity during in utero transfer to other units for gestations and PTD in a general and unselected obstetric population.

Fetal fibronectin

Fetal fibronectin (fFN) is a basement membrane protein produced by the fetal membranes, which binds the placenta and membranes to the decidua. It is normally present in cervicovaginal fluid until about 20 weeks’ gestation as the gestational sac attaches itself to the uterus. Beyond 20 weeks fFN in the cervicovaginal fluid is amniocentesis following pPROM showed that the frequency of positive amniotic fluid is 25–40% with the risk of a positive culture inversely related to the gestational age at which pPROM occurred. Women with intrauterine infection have shorter latency than non-infected women, and infants born with sepsis have a fourfold increase in mortality than infants born without sepsis (Cotton et al. 1984). These findings have fuelled interest in the use of antibiotics to prevent pPROM in women at risk, to increase latency after pPROM, and as prophylaxis against neonatal morbidity such as oxygen dependency, intraventricular haemorrhage, necrotizing enterocolitis, neonatal sepsis, and mortality. Aetiology and pathophysiology

The tensile strength of the membranes is mainly due to types III and IV collagen secreted by the epithelial cells of the amniotic membrane. In recent years, our understanding of the cellular and molecular factors that govern the structural integrity of fetal membranes and their regulation has increased and it is now clear that only a proportion of pPROM cases are infection driven. Other pathological processes such as choriodecidual fusion defects (Bryant-Greenwood and Millar 2000), fetal growth dysregulation (Cooperstock et al. 2000), activation of membrane apoptosis (Fortunato et al. 2000), upregulation of matrix metal-loproteinases, and inhibition of tissue inhibitors of matrix metalloproteinases (Fortunato 1999), nutritional factors (Barrett 1994), and smoking (Barrett 1991) may be important in a significant proportion of cases of pPROM. Diagnosis and initial assessment

The diagnosis of pPROM is made by maternal history, speculum examination and simple bedside tests. Although maternal history has an accuracy of 90% for the diagnosis of pPROM (Gaucherand 1995), it is good practice to confirm the diagnosis before applying the label of pPROM. The presence of a pool of amniotic fluid in the posterior fornix on speculum examination is confirmatory of pPROM. There may be a role for nitrazine pH-based paper testing when there is a very small amount of fluid in the posterior fornix and the observer is uncertain. However, the nitrazine test is not specific and has a false-positive rate of 17% (Gaucherand et al. 1995). The pH of vaginal fluid changes towards the alkaline range in the presence of bacterial vaginosis, other vaginitis, contamination with cervical secretion, blood, semen, or urine. In doubtful cases the patient may be asked to cough gently while visualizing the external cervical os for any trickle of amniotic fluid. An extended pad test is also useful. A panel of newer tests has been evaluated for pPROM, including fetal fibronectins and raised insulin-like growth factor binding protein-1 (IGFBP-1) in cervicovaginal secretions. These have sensitivities of 94% and 75%, respectively, and specificities of 97% (Rutanen 1993). Spontaneous rupture of membranes during the second, and early third trimesters is usually associated with a near total loss of the entire amniotic fluid pool. Therefore, ultrasound scan evidence of marked oligohydramnious or anhydramnious is highly suggestive of a diagnosis of pPROM in this context. Such an ultrasound examination should be extended to exclude fetal anomaly, evaluate the fetal growth and development, and estimate the fetal weight and presentation.

A digital vaginal examination should be avoided following a diagnosis of pPROM, unless there is a strong suspicion of labour or imminent delivery. Recent studies have shown that two or fewer digital vaginal examinations were associated with a shorter latency period but no increase in fetal or maternal infectious morbidity (Alexander et al. 2000). Thus, if one or two digital vaginal examinations were done after pPROM, this should not constitute an indication to abandon conservative management or pursue an immediate induction of labour for fear of increased risk of fetomaternal infectious morbidity. Current management of pPROM

In many units, women with pPROM are admitted into the hospital and managed conservatively until 37 completed weeks in an attempt to increase fetal maturity. Conservative management involves 4-hourly measurements of maternal temperature, heart rate, respiratory rate, and blood pressure, daily cardiotocographs (CTGs), weekly, twice, or thrice weekly maternal white cell counts, C-reactive protein assays, and culture of vaginal swabs, all in an effort to detect intrauterine infection or chorioamnionitis. However, with histological chorioamnionitis maternal inflammatory markers are raised in only 10–15% of cases (Romero et al. 1989), suggesting that maternal markers are not sufficiently sensitive to guide clinical decisions. Furthermore, the micro-organisms usually associated with chorioamnionitis are subpathogenic, non-pyrogenic, and are often not detected on routine microbiological culture methods. For prognosis, it is fetal rather than maternal evidence of inflammation that is predictive of adverse neonatal outcome. However, the search for evidence of fetal inflammation by amniocentesis and/or cordocentesis is not routine practice and its role in reducing the risk of neonatal complications has not been adequately evaluated. Critique of management strategies

The majority of women with infection-driven pPROM will deliver within 5 days; therefore, the value of inpatient management beyond 5 days is questionable. Outpatient care with instruction for the patient to take her own temperature and be reviewed once or twice weekly in hospital is reasonable. She should, however, be discouraged from vaginal intercourse, protected or not, and any form of intravaginal cleansing. Immersion in plain bath water is not associated with an increase in infectious morbidity. A oneoff vaginal swab for pathogens, particularly group B streptococcus will suffice. There is little or no correlation between the organisms that cause amniotic fluid infection/chorioamnionitis and those isolated from the lower genital tract. Nursing women with pPROM in a head-down tilt position is unnecessary and may encourage a stagnant pool of amniotic fluid and cervicovaginal secretions with a potential for encouraging bacterial growth and multiplication. Although fetal CTG is recommended as part of the surveillance, there are no specific or reliable CTG patterns that are predictive of fetal inflammation or sepsis until very late, and neurological injuries may occur without significant CTG changes. Clinical chorioamnionitis defined as maternal fever (temperature ≥38°C) and the presence of any two or more of the following, maternal or fetal tachycardia, uterine tenderness, foul-smelling or purulent vaginal discharge, maternal leucocytosis, or raised C-reactive protein, is poorly predictive of histological chorioamnionitis, which has been shown to be more predictive of abnormal neonatal cerebral outcomes including periventricular echodensity/echolucency, ventriculomegaly, intraventricular haemorrhage, and seizures (De Felice 2001).

Timing of delivery

Expectant management until 37 weeks to improve fetal maturity is historical and based on the assumption that prolongation of pregnancy automatically translates to better fetal maturity and neonatal outcome. The risks of cord events including acute cord compression, cord prolapse, or ascending infection are not insignificant. The risks of prematurity-related morbidity including respiratory distress syndrome, necrotizing enterocolitis, grades 3–4 intraventricular haemorrhage, and mortality, diminish significantly beyond 32–34 weeks and that neonatal survival at 34 weeks in tertiary units is similar to 37–40 weeks. The increase in survival per additional week of conservative management is less than 1%.

Studies evaluating the risk–benefit analysis of induction of labour at 34 weeks found similar vaginal delivery rates, and no increase in the risk of instrumental vaginal delivery or Caesarean section (Naef et al. 1998). On the other hand, these studies documented an excess incidence of ascending infection, neonatal sepsis, cord prolapse or compression, fetal demise, and longer hospital stay in cases managed conservatively (Naef et al. 1998; Grable 2002). Therefore, the benefits of delivery at 34 weeks outweigh the risks of conservative management without increasing obstetric intervention. This balance, however, is in favour of expectant management prior to 32 weeks as delivery before 32 weeks’ gestation is associated with a significant risk of gestational age-related morbidity and mortality. Therefore, unless there are concerns regarding fetal well-being, clinical or biochemical evidence of infection, women with pPROM remote from term should be managed conservatively to prolong gestation until 34 weeks to reduce the risk of gestational age related morbidity and mortality.

Antibiotic therapy to prolong latency and prevent neonatal morbidity after pPROM

Evidence from meta-analysis of randomized trials suggests that antibiotic therapy (ampicillin and/or erythromycin) delayed preterm delivery, and reduced maternal and neonatal morbidity (Mercer et al. 1994; Kenyon et al. 2004).

Routine antibiotic is therefore recommended for women with pPROM. Routine antibiotic therapy presumes an infectious aetiology, lacks guidance from microbiological cultures and sensitivity, and is based on the belief that the antibiotic somehow prevents or reverses fetal damage. Widespread use has led to an increase in erythromycin-resistant organisms even in the years leading up to the publication of the ORACLE trial (Pearlman et al. 1998; et al. 2003). This trend was attributed to increased use of erythromycin for prophylaxis against Group B streptococcus for women who were allergic to penicillin and is likely to escalate with its increased use for pPROM. Tocolysis

Tocolysis may be applied prophylactically to prevent the onset of uterine contractions and labour in women with pPROM, or used therapeutically to abolish uterine contractions and labour after pPROM. The use of tocolysis should be individualized and restricted to those situations where there are no clinical or biochemical evidence of infection and a course of corticosteroids needed to be completed, or to allow the transfer of the woman to a tertiary centre. The choice of a tocolytic agent is a matter for local guidelines as the efficacies of the available agents are broadly similar. However, the β-adrenoceptor agonists have become less popular because of their marked cardiovascular side-effects. Corticosteroid therapy

Initial concerns that corticosteroids may increase the risks of chorioamnionitis, postpartum endometritis, and neonatal sepsis are not supported by current evidence. Antenatal steroids reduced the risks of respiratory distress syndrome, intraventricular haemorrhage, and necrotizing enterocolitis (Harding et al. 2001). These substantial reductions in the risk of major gestational age-related morbidity translate to a significant reduction in neonatal mortality. There are few data on whether using the same dose of corticosteroid, this magnitude of benefit may also accrue for twins and other higher order pregnancies with pPROM, because of greater maternal volume of distribution. In diabetic women, the administration of corticosteroids may result in the loss of glycaemic control. The risk of this has to be carefully balanced with the potential benefit. Therefore in diabetic women with pPROM near term for example ≥32–34 weeks or in whom fetal lung maturation can be demonstrated, the value of steroid administration is questionable. Below 32 completed weeks of gestation, consideration should be given for sliding scale insulin/glucose infusion for 48–96 hours during the course of antenatal prophylactic steroid. Intramuscular betamethasone 12 mg, 24 hours apart is preferable to dexamethasone 12 mg, 12 hours apart. Betamethasone has a stronger evidence base and unlike dexamethasone, is not associated with necrotizing enterocolitis. The role of amniocentesis

Studies of amniocentesis in pPROM women show that up to 40% (more with DNA amplification techniques) will have positive amniotic fluid cultures, and/or raised inflammatory markers at presentation, with the proportion increasing with latency. Fetal host inflammatory response rather than amniotic fluid colonization or maternal response is correlated with adverse neonatal outcome. Amniocentesis, culture of amniotic fluid and determination of the presence or absence of fetal host response may allow clinicians to select and triage cases for conservative or aggressive management. There is no evidence, however, that characterization of the amniotic fluid inflammatory status to guide management improved perinatal outcome. The timing of fetal injury is unknown and it is plausible that by the time women present with pPROM, it is already too late to reverse established inflammatory cascade. The mechanisms through which ampicillin and/or erythromycin therapy delayed preterm delivery, and reduced maternal and neonatal morbidity, remain unknown. Although the eradication of intrauterine infection, reduction/prevention of host inflammatory response, or prevention of ascending infection from the lower genital tract have all been proposed, Gomez et al. (2007) showed that antibiotic treatment very rarely eradicated microbial invasion of the amniotic cavity in patients with pPROM. An overwhelming 86% of pPROM patients with positive amniotic fluid culture and 83% with intra-amniotic inflammation maintained the same microbiological/inflammatory profile respectively, despite aggressive antibiotic therapy for 10–14 days (Gomez et al. 2007). This is consistent with data that showed poor transplacental transfer of macrolide antibiotics (Witt et al. 2003). The study also found that women with negative amniotic fluid culture or inflammation at admission developed microbial invasion of the amniotic cavity despite antibiotic therapy. Further reading

Alexander JM, Mercer BM, Miodovnik M, et al. The impact of digital cervical examination on expectantly managed preterm rupture of membranes. Am J Obstet Gynecol 2000;183:1003–7.

Barrett B, Gunter E, Jenkins J, Wang M. Ascorbic acid concentration in amniotic fluid in late pregnancy. Biol Neonate 1991;60:333–5.

Barrett BM, Sowell A, Gunter E, Wang M. Potential role of ascorbic acid and beta-carotene in the prevention of preterm rupture of fetal membranes. Int J Vitam Nutr Res 1994;64:192–7.

Bryant-Greenwood GD, Millar LK. Human fetal membranes: their preterm premature rupture. Biol Reprod 2000;63:1575–9.

Cooperstock MS, Tummaru R, Bakewell J, Schramm W. Twin birth weight discordance and risk of preterm birth. Am J Obstet Gynecol 2000;183:63–7.

Cotton DB, Hill LM, Strassner HT, et al. Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol 1984;63:38–43.

De Felice C, Toti P, Laurini RN, et al. Early neonatal brain injury in histologic chorioamnionitis. J Pediatr 2001;138:101–4.

Fortunato SJ, Menon R, Bryant C, Lombardi SJ. Programmed cell death (apoptosis) as a possible pathway to metalloproteinase activation and fetal membrane degradation in premature rupture of membranes. Am J Obstet Gynecol 2000;182:1468–76.

Fortunato SJ, Menon R, Lombardi SJ. MMP/TIMP imbalance in amniotic fluid during PROM: an indirect support for endogenous pathway to membrane rupture. J Perinat Med 1999;27:362–8.

Gaucherand P, Guibaud S, Awada A, Rudigoz RC. Comparative study of three amniotic fluid markers in premature rupture of membranes: fetal fibronectin, alpha-fetoprotein, diamino-oxydase. Acta Obstet Gynecol Scand 1995;74:118–21.

Gomez R, Romero R, Nien JK, et al. Antibiotic administration to patients with preterm premature rupture of membranes does not eradicate intra-amniotic infection. J Matern Fetal Neonatal Med 2007;20:167–73.

Grable IA. Cost-effectiveness of induction after preterm premature rupture of the membranes. Am J Obstet Gynecol 2002;187:1153–8.

Harding JE, Pang J, Knight DB, Liggins GC. Do antenatal corticosteroids help in the setting of preterm rupture of membranes? Am J Obstet Gynecol 2001;184:131–9.

Kenyon S, Boulvain M, Neilson J. Antibiotics for preterm rupture of the membranes: a systematic review. Obstet Gynecol 2004;104:1051–7.

Manning SD, Foxman B, Pierson CL, et al. Correlates of antibiotic-resistant group B streptococcus isolated from pregnant women. Obstet Gynecol 2003;101:74–9.

Mercer BM, Miodovnik M, Thurnau GR, et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. JAMA 1997;278:989–95.

Naef RW, III, Allbert JR, Ross EL, et al. Premature rupture of membranes at 34 to 37 weeks’ gestation: aggressive versus conservative management. Am J Obstet Gynecol 1998;178:126–30.

Pearlman MD, Pierson CL, Faix RG. Frequent resistance of clinical group B streptococci isolates to lindamycin and erythromycin. Obstet Gynecol 1998;92:258–61.

Romero R, Sirtori M, Oyarzun E, et al. Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes. Am J Obstet Gynecol 1989;161:817–24.

Rutanen EM, Pekonen F, Karkkainen T. Measurement of insulin-like growth factor binding protein-1 in cervical/vaginal secretions: comparison with the ROM-check Membrane Immunoassay in the diagnosis of ruptured fetal membranes. Clin Chim Acta 1993;214:73–81.

Witt A, Sommer E, Cichna M, et al. Placental passage of clarithromycin surpasses other macrolide antibiotics. Am J Obstet Gynecol 2003;188:816–9.

Prolonged pregnancy Definition

Prolonged or post-term pregnancy has traditionally been defined as the pregnancy continuing beyond two weeks after the expected date of delivery. Prolonged pregnancy is known to be associated with risks of intrauterine growth restriction, intrauterine death, macrosomia, and an increased incidence of operative deliveries. Confirmation of prolonged pregnancy

It is essential to ascertain the expected date of delivery, as dating error is the commonest cause of prolonged pregnancy. The estimated date of delivery, in normal pregnancies, is calculated as 280 days (40 weeks) from the date of the last menstrual period (assuming regular 28-day menstrual cycle). This is more likely to be accurate when

• there was no hormonal contraceptive use or breastfeeding for 3 months preceding the last menstrual period

• if the date of last menstrual period was certain

• when it matches with the ultrasound estimated date of delivery.

• Where the date of the last menstrual period was not available or uncertain or differs from the dating from ultrasound parameters in the absence of chromosomal or other abnormalities, the estimated date of delivery is calculated from the following ultrasound parameters:

• from crown–rump length (CRL) measured between 11 and 14 weeks

• from head circumference in the second trimester

It is difficult to ascertain the expected date of delivery by ultrasound parameters after 20–24 weeks. Hence, National Institute for Health and Clinical Excellence (NICE) guidelines recommend that all pregnant women in the UK should be offered an ultrasound scan between 11 and 14 weeks, and that the due date estimated is based on this scan regardless of the menstrual dates. Incidence

Incidence of prolonged pregnancy reduced from 10.3% to 3.7% when the date was estimated from an ultrasound before 24 weeks. A meta-analysis found reduced rates of induction of labour for post-term pregnancy (OR 0.68, 95% CI 0.57–0.82) among women who underwent sonographic gestational age assessment in early pregnancy (before 24 weeks). Risk factors for prolonged pregnancy

Primiparity and prior post-term pregnancy are the most common identifiable risk factors. Placental sulphatase deficiency is a rare postulated cause. Male gender has been shown to be predisposing to prolongation of pregnancy. The reduced risk of recurrence of post-term birth observed with the change in the male partner suggests that the timing of birth may be determined by paternal genes. Being parous appears to have a protective effect on fetal mortality in prolonged pregnancy. Risks of prolonged pregnancy

With continued fetal growth, there is a higher risk of big babies. This increases the chances of fetopelvic disproportion and shoulder dystocia. The amniotic fluid volume gradually decreases, increasing the risk of intrapartum cord compression. The ageing placenta may fail to support the baby. Rate of meconeum passage is high. Perinatal mortality

Data derived from accurately dated pregnancies show an increased perinatal mortality rate from 41 weeks. The rate increases from 2–3/1000 at 40 weeks to 4–7/1000 after 42 weeks. The rates of fetal loss per 1000 ongoing pregnancies are 0.7, 2.4 and 5.8 at 37, 40 and 43 weeks. Post-term babies who are small for gestational age are at an increased risk of perinatal death compared with those who are appropriately grown. Perinatal morbidity

There is an increased risk of meconium aspiration syndrome, macrosomia, low Apgars, Neonatal hypoglycemia, seizures, respiratory distress, and admission to neonatal intensive care unit. Labour abnormalities

The incidence of prolonged labour, abnormal fetal heart rate pattern, operative delivery, shoulder dystocia, perineal trauma, and postpartum haemorrhage is increased in prolonged pregnancies (Table 9.14.1). Assessment of post-dated pregnancy

Thorough history, examination, and appropriate investigations should be undertaken to exclude complications such as small for gestational age babies, congenital anomalies, malpresentation, pre-eclampsia, etc. NICE guidelines recommend that vaginal examination and membrane sweeping should be offered to all nulliparous women after 40 weeks and parous women at 41 weeks; this has been shown to reduce the rate of post-term pregnancy. Vaginal examination will aid in assessing the favourability of the cervix using Bishop’s score. Membrane sweeping is a minimally invasive method which helps in the onset of spontaneous labour. Monitoring

The goal of monitoring is to reduce the risk of fetal death by detecting signs of hypoxic fetal compromise. At the same time, the clinician has to balance this against the risks of unnecessary intervention induced labour. There is insufficient evidence to recommend routine monitoring between 40 and 42 weeks. After 42 weeks, twice weekly fetal monitoring with cardiotocographic assessment (non-stress test) and amniotic fluid assessment are recommended as a good practice point. However, there is limited evidence to showing benefit of these tests. Doppler assessment of umbilical artery is not shown to be useful in monitoring post-dated pregnancies. In general, there is insufficient evidence to recommend any particular monitoring in post-term pregnancies to reduce the adverse outcome.

Table 9.14.1 Risks of post-term pregnancies (data from Eden et al. 1987)

Management

The Cochrane review (Gülmezoglu et al. 2006) concluded that routine induction after 41 weeks reduces perinatal mortality without any increase in the Caesarean section rate. It would be prudent to discuss the risks and benefits of labour induction versus expectant management at 41 weeks so that the woman can make an informed choice. If the woman chooses to wait spontaneous labour onset beyond 42 weeks, twice weekly fetal monitoring is recommended. Methods of induction of labour

This has been summarized in section 10.9 Induction of labour. Risk of recurrence

It is estimated to be 20%, increasing with increasing gestational age at index pregnancy (30% for a gestational age of 44 weeks). Practice points

1. Routine pregnancy dating using early ultrasonography reduces the incidence of post-term pregnancies.

2. Appropriate fetal wellbeing tests in prolonged pregnancy are largely unknown.

3. Small fetuses in prolonged pregnancies are at a higher risk of serious adverse outcome.

4. Currently, the only policy of demonstrable benefit is induction of labour after 41 weeks, but the exact timing is still uncertain. Further reading

Agency for healthcare research and quality. Management of prolonged pregnancy. Evidence report/Technology assessment. Number 53.

Crowley P. Interventions for preventing or improving the outcome of delivery at or beyond term. Cochrane Database Syst Rev 2006; 4: CD000170.

Eden R, Seifert L, Vinegar A, Spellacy W. Perinatal characteristics of uncomplicated postdate pregnancies. Obstet Gynecol 1987;69:296–9.

Gülmezoglu AM, Crowther CA, Middleton P. Induction of labour for improving birth outcomes for women at or beyond term. Cochrane Database Syst Rev 2006; 4: CD004945.

Hilder L, Costeloe K, Thilaganathan B. Prolonged pregnancy: evaluating gestation-specific risks of fetal and infant mortality. Br J Obstet Gynaecol 1998;105:169–73.

Hilder L, Sairam S, Thilaganathan B. Influence of parity on fetal mortality in prolonged pregnancy. Eur J Obstet Gynecol Reprod Biol 2007;132:167–70.

NICE guidelines. Antenatal care for the healthy pregnant women. National Colloborating Centre for women’s and children’s health. March 2008.

NICE guidelines. Induction of labour. National Colloborating Centre for women’s and children’s health. July 2008.

Olsen A, Basso O, Olsen J. Risk of recurrence of prolonged pregnancy. BMJ 2003; 326: 476.

Puerperal sepsis Definition

The International Classification of Diseases (ICD-10) defines puerperal fever as a rise in temperature of greater than 38.0°C sustained for more than 24 hours or recurring between the end of the first and tenth day of childbirth, miscarriage, or termination of pregnancy. It can develop into puerperal sepsis, which is a serious and life threatening septicaemia. The United Kingdom Confidential Enquiry into Maternal and Child Health reported that in 2003–5 genital tract sepsis accounted for 14% of direct causes of maternal death, making puerperal fever a significant factor in maternal death. The most common infection causing puerperal fever is genital tract sepsis. Other types of infection that can lead to sepsis after childbirth include urinary tract infection, mastitis, and respiratory tract infection. Aetiology

It is a polymicrobial condition that affects a small minority of women, suggesting that the pathogenesis involves more than just a source of potentially pathogenic bacteria. Endometritis is most commonly caused by Staphylococcus aureus and group A streptococcus, specifically Streptococcus pyogenes, which is responsible for most cases of severe hemolytic streptococcal illness although other types B, C, D, and G may also cause infection. Group B streptococcus usually causes less severe maternal disease. Other causal organisms, in order of prevalence, include staphylococci, coliform bacteria, anaerobe bacteria, chlamydia bacteria, mycoplasma, and, very rarely, Clostridium welchii. Endometritis

Endometritis is the commonest puerperal infection and usually presents within 5 days of delivery.

Risk factors

• Caesarean section (27% versus 1.2% in women who had vaginal delivery)

• Multiple vaginal examinations during labour

• Prolonged rupture of membranes

• Use and duration of internal monitoring devices

• Prolonged labour

• Group B streptococcal colonisation

• Anaemia, diabetes mellitus, obesity.

Diagnosis

Criteria for diagnosis include fever, with or without chills and rigors, uterine tenderness, with or without abdominal pains, purulent or foul-smelling lochia, leucocytosis, and exclusion of another focus of infection. There may be tacchycardia. Localizing signs may be absent if the infection is due to group A or B streptococcus. Obtain cervical and vaginal samples for culture.

Treatment

If febrile and unwell, use intravenous broad-spectrum antibiotics with anaerobic cover, for example cephalosporin or clindamycin and gentamycin. Septic pelvic thrombophlebitis

This is thought to be due to bacterial injury to the pelvic (ovarian) venous endothelium. The diagnosis should be considered in any patient with a persistent temperature despite appropriate antibiotic therapy and prior soft tissue pelvic infection.

Clinical features

• Persistent fevers may be the only presentation

• Progressively worsening abdominal pain usually right more than left

• Nausea, vomiting or abdominal distension may be present

• Bowel sounds may be normoactive or absent

• Tacchycardia

• Tacchypnoea and respiratory distress if pulmonary embolus has occurred

• The thrombosed ovarian vein (usually right) may be palpable as an abdominal or adnexal mass.

Investigations

• Ultrasound scan

• CT scan

Treatment

• Broad-spectrum antibiotic therapy

• Anticoagulation with heparin was a traditional adjunct to therapy but this is no longer recommended

• Surgical ligation/excision of the affected vein is reserved for patients with acute abdomen or not responding to medical therapy Urinary tract infection

This is a common cause of postpartum pyrexia and is usually caused by Escherichia coli, although enterococci, group B streptococci and other gram-negative aerobic bacilli may occasionally be responsible. Symptoms include dysuria, frequency, nocturia, fever, backache, and physical examination may reveal tenderness in the renal angles. A clean catch specimen of urine for culture is helpful in diagnosis. Sterile pyuria may reflect bladder inflammation from trauma during labour and delivery.

Risk factors

• Physiological hydroureter of pregnancy

• Asymptomatic bacteriuria

• Intrapartum catheterization.

Treatment

Parenteral cephalosporin and gentamycin initially until urine cultures and antibiotic sensitivities become available Mastitis and breast abscess

Staphylococcus aureus is the main causative agent of sporadic, epidemic, and endemic mastitis. Fever, malaise, and breast pain and tenderness are the usual presenting features. Breast abscess may develop in untreated cases.

Treatment

A penicillinase-resistant penicillin such as flucloxacillin or erythromycin should be administered. Other measures include breast support, ice packs, and analgesics. Breastfeeding should continue unless abscess develops. Wound and episiotomy infections

Around 5–15% of Caesarean section wounds become infected depending on the definition of wound infection used. The presence of erythema, induration, pain, and fluid exudate are suggestive signs. If the wound breaks down, debridement, and secondary closure is now recommended instead of the traditional approach of debridment and dressing, and allowing healing by secondary intention. Clinicians should maintain a high index of suspicion in order to recognize life-threatening wound complications such as necrotizing fasciitis, clostridial myonecrosis (gas gangrene), and non-clostridial bacterial synergistic gangrene (Meleney gangrene).

A simple episiotomy infection usually presents with localized erythema, oedema, and exudate, which are limited to the surrounding skin and subcutaneous tissue. If the findings are more extensive, a deeper infection may be present. The wound should be opened, explored, drained, and debrided, and appropriate antibiotics administered.

Most of these will heal by granulation but if perineal muscles or the anal sphincter is involved, the wound should be resutured once the infection settles down, in about 5–10 days. The patient should avoid sexual intercourse and have sitz baths three or four times daily. Further reading

Gwyneth Lewis (ed.). Saving Mothers’ Lives: Reviewing maternal deaths to make motherhood safer–2003–2005. The Seventh Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. www.cemach.org.uk/getattachment/8f5c1ed8-fdf3–489b-a182-e53955bec07b/Saving-Mothers–Lives-2003–2005_full.aspx:+CEMACH. page 97.