Obstetrics & Gynaecology

Key Facts

Antenatal screening is a public health programme offering all pregnant women tests to assess risk of fetal abnormality and maternal infection. It enables early detection of conditions where intervention, treatment, or informed planning may improve outcomes. Screening is not diagnostic - it identifies individuals at higher risk who may benefit from further diagnostic testing.

Epidemiology

Down syndrome (T21) affects approximately 1 in 800-1,000 births (incidence before screening). Edwards syndrome (T18) ~1 in 6,000; Patau syndrome (T13) ~1 in 10,000. The UK FASP screens approximately 600,000+ pregnancies annually. Neural tube defects have a prevalence of approximately 1 in 1,000 pregnancies (significantly reduced by folic acid supplementation). HIV prevalence in pregnant women in the UK is approximately 1 in 500.

Aetiology

Conditions screened for have various aetiologies:

• Chromosomal (T21, T18, T13): Usually sporadic non-disjunction; risk increases with maternal age
• Structural anomalies: Multifactorial; some genetic (cardiac defects, renal anomalies)
• Neural tube defects: Folate deficiency is a major risk factor; folic acid supplementation reduces risk by ~70%
• Infections: HIV, hepatitis B, syphilis - transmission risk to fetus without intervention

Pathophysiology

Screening markers:

• Nuchal translucency: Increased subcutaneous fluid at back of fetal neck; associated with T21, T18, T13, Turner syndrome, cardiac defects
• β-hCG: Elevated in T21, reduced in T18/T13
• PAPP-A: Reduced in T21, T18, T13
• AFP: Elevated in neural tube defects, abdominal wall defects; reduced in T21
• Cell-free fetal DNA (NIPT): Fragments of fetal DNA (from placental trophoblast) circulate in maternal blood from ~10 weeks; can be analysed for chromosome copy number

Screening Schedule

• Booking bloods (by 10 weeks): Blood group, antibodies, FBC, HIV, hepatitis B, syphilis
• Combined screening (11+0 to 14+1 weeks): Nuchal translucency + serum markers
• Anomaly scan (18+0 to 20+6 weeks): Structural assessment of 11 conditions
• 28 weeks: Repeat antibody screen

Positive Screening Result Discussion

• Results expressed as probability (e.g., 1:100 for T21)
• Screen-positive threshold: ≥1:150 for combined/quadruple test (offered further testing)
• Counselling about diagnostic options (amniocentesis, CVS) including risks and implications
• Non-directive approach - support whatever decision the parents make

Conditions Screened by Anomaly Scan

• Anencephaly, open spina bifida, cleft lip, diaphragmatic hernia, exomphalos, gastroschisis, serious cardiac abnormalities, bilateral renal agenesis, lethal skeletal dysplasia, Edwards syndrome (T18), Patau syndrome (T13)

Red Flags

• Very high-risk screening result (e.g., 1:5 for T21) - urgent counselling and diagnostic testing
• Major structural anomaly on scan - fetal medicine referral
• Positive HIV, hepatitis B, or syphilis - immediate specialist management pathway
• Significantly raised AFP - consider neural tube defect, abdominal wall defect, or placental pathology

Bedside

• Nuchal translucency USS (11-14 weeks): NT ≥3.5mm is significantly increased risk; combined with maternal age and serum markers for risk calculation

Bloods

• Combined test (11-14 weeks): NT + free β-hCG + PAPP-A - T21 detection ~85%, 5% FPR
• Quadruple test (15-20 weeks): AFP + total β-hCG + uE3 + inhibin A - T21 detection ~80%, 5% FPR
• NIPT (from 10 weeks): Maternal blood sample; analyses cell-free fetal DNA; >99% sensitivity for T21, ~97% for T18/T13; FPR <0.1%
• Booking screening bloods: HIV antibody, HBsAg, syphilis (TPHA/EIA), blood group + antibodies, FBC
• Haemoglobinopathy screening: At booking - sickle cell and thalassaemia (universal or targeted based on ethnicity)

Imaging

• Dating scan (11-14 weeks): CRL measurement, viability, multiple pregnancy, NT
• Anomaly scan (18-20+6 weeks): Systematic structural assessment; sensitivity varies by condition (~50-60% for cardiac defects, >95% for anencephaly)
• Fetal echocardiography: If raised NT, family history CHD, maternal diabetes, or anomaly scan concern

Special Tests

• Amniocentesis (from 15 weeks): Aspiration of amniotic fluid - karyotype, microarray, specific gene testing; miscarriage risk ~0.5-1%
• CVS (from 11 weeks): Placental tissue sampling - earlier diagnosis; miscarriage risk ~0.5-1%
• QF-PCR (quantitative fluorescence PCR): Rapid result (24-48h) for common aneuploidies (T21, T18, T13, sex chromosomes)

Non-pharmacological

• Pre-test counselling: Explain what screening involves, what it detects, limitations, and implications of results
• Informed consent: Screening is voluntary; document consent/declination
• Post-result counselling: If screen-positive, provide balanced information; discuss diagnostic testing options
• Specialist referral: Fetal medicine for abnormal screening/scan findings
• Psychological support: Access to counselling service for parents facing difficult decisions
• Multidisciplinary planning: If fetal anomaly confirmed - paediatric surgery, neonatology, genetics, palliative care as appropriate

Pharmacological

• HIV: Start antiretroviral therapy to reduce vertical transmission to <0.5% (aim for undetectable viral load)
• Hepatitis B: HBIG + hepatitis B vaccine for neonate at birth; maternal antiviral if high viral load
• Syphilis: IM benzathine penicillin 2.4 million units (single dose for early; 3 weekly doses for late) - treats maternal infection and prevents congenital syphilis
• Anti-D: If invasive diagnostic procedure performed (amnio/CVS) in Rh-negative woman
• Folic acid: 5mg daily if increased NTD risk (previous NTD, epilepsy medication, diabetes)

Surgical/Interventional

• Amniocentesis: USS-guided transabdominal needle aspiration of amniotic fluid
• CVS: Transabdominal or transcervical biopsy of chorionic villi
• Fetal therapy: In utero repair of spina bifida (MOMS trial), laser for twin-twin transfusion syndrome, fetal blood transfusion for alloimmune anaemia
• Termination of pregnancy: Available up to 24 weeks, or beyond if substantial risk of serious handicap (Ground E, Abortion Act 1967)

Referral Criteria

• Screen-positive result - fetal medicine for counselling and diagnostic testing
• Structural anomaly on scan - fetal medicine specialist
• Positive infectious disease screen - respective specialist (HIV, hepatology, GUM)
• Previous affected pregnancy or family history - genetics/fetal medicine for preconception counselling

• Combined screening: ~85% detection rate for T21 with 5% FPR
• NIPT: >99% detection rate for T21; FPR <0.1%; reduces need for invasive testing by ~50%
• Amniocentesis/CVS: Diagnostic accuracy essentially 100% for chromosomal disorders
• Anomaly scan: Detection rates vary - ~50-60% for cardiac defects, >95% for anencephaly, ~80-90% for spina bifida
• HIV screening and treatment: Reduces vertical transmission from ~25% to <0.5%
• Hepatitis B: Neonatal vaccination + HBIG reduces transmission from ~90% to <5%
• Syphilis treatment: Prevents congenital syphilis in ~98% of treated cases
• Neural tube defects: Folic acid supplementation reduces risk by approximately 70% (MRC Vitamin Study 1991)

Comparison of Screening Tests for Chromosomal Abnormalities

11 Conditions Screened at Anomaly Scan (FASP)

Key Facts

Hyperemesis gravidarum (HG) represents the severe end of the spectrum of nausea and vomiting in pregnancy. It can cause significant morbidity, including dehydration, electrolyte imbalance, nutritional deficiency, and psychological distress. Early aggressive management improves outcomes.

Epidemiology

NVP affects approximately 70-80% of pregnant women. Hyperemesis gravidarum (severe, requiring treatment) affects approximately 1-3%. Peak onset is 6-8 weeks, peak severity at 8-12 weeks, with resolution by 16-20 weeks in most. Approximately 10% have symptoms beyond 20 weeks, and rarely symptoms persist throughout pregnancy. HG is the most common cause of hospital admission in early pregnancy.

Aetiology

The exact cause is unclear; likely multifactorial:

• hCG: Highest correlation - hCG peaks at 10-12 weeks, mirroring symptom peak; explains increased risk with molar pregnancy and multiple pregnancy
• Oestrogen/progesterone: Hormonal effects on GI motility and chemoreceptor trigger zone
• Helicobacter pylori: Association in some studies
• Genetic: Strong familial tendency; genome-wide association studies identify GDF15 and IGFBP7 as key mediators
• Psychological: Stress and anxiety exacerbate symptoms (but are not causative)

Pathophysiology

Persistent vomiting leads to:

• Dehydration: Volume depletion → pre-renal AKI
• Metabolic alkalosis: Loss of gastric HCl (similar to pyloric stenosis)
• Hypokalaemia: Renal potassium wasting to compensate for alkalosis
• Hyponatraemia: Volume depletion + excessive ADH secretion
• Ketonuria/ketosis: Starvation metabolism - fat mobilisation
• Thiamine deficiency: Can develop rapidly (within 2-3 weeks of vomiting); leads to Wernicke's encephalopathy (confusion, ataxia, ophthalmoplegia) - a medical emergency

Symptoms

• Persistent, severe nausea and vomiting (multiple times per day)
• Inability to tolerate oral food or fluids
• Weight loss >5% of pre-pregnancy weight
• Ptyalism (excessive salivation)
• Sensitivity to smells and food aversions

Signs

• Dehydration: Dry mucous membranes, reduced skin turgor, tachycardia, postural hypotension
• Ketonuria on dipstick (2+ or more)
• Weight loss documented from pre-pregnancy or early pregnancy weight

Psychological Impact

• Significant depression, anxiety, and social isolation
• May consider termination of a wanted pregnancy due to symptom severity
• Post-traumatic stress symptoms in severe cases

Red Flags

• Confusion, ataxia, nystagmus/ophthalmoplegia - Wernicke's encephalopathy (give thiamine immediately)
• Severe hypokalaemia (K⁺ <2.5 mmol/L) - risk of cardiac arrhythmia
• Haematemesis - consider Mallory-Weiss tear from forceful vomiting
• Thyrotoxicosis symptoms - gestational thyrotoxicosis (hCG-mediated) occurs in ~60% of HG
• Abdominal pain or fever - exclude other diagnoses (UTI, appendicitis, pancreatitis)

Bedside

• Weight: Compare to pre-pregnancy or early pregnancy weight - >5% loss supports diagnosis
• Urine dipstick: Ketonuria (grade severity); exclude UTI
• Vital signs: Tachycardia, postural hypotension indicating dehydration
• PUQE score (Pregnancy-Unique Quantification of Emesis): Validated severity assessment tool

Bloods

• U&Es: Hypokalaemia, hyponatraemia, raised urea/creatinine (dehydration)
• FBC: Haemoconcentration
• LFTs: Mildly elevated transaminases in ~50% of HG
• TFTs: Gestational thyrotoxicosis (suppressed TSH, mildly raised fT4) - occurs in ~60% due to hCG cross-reactivity with TSH receptor; usually does not require treatment
• Calcium: Hypercalcaemia can cause vomiting (exclude)
• Amylase/lipase: If pancreatitis suspected

Imaging

• USS: Confirm viability, exclude molar pregnancy, multiple pregnancy

Special Tests

• MSU MC&S: Exclude UTI (can co-exist or mimic HG)
• Serum β-hCG: If molar pregnancy suspected (very high levels)

Non-pharmacological

• Avoid triggers: Identify and avoid food/smell triggers
• Dietary advice: Small, frequent, bland meals; ginger products; dry crackers before rising
• Acupressure: P6 (Nei-Kuan) wrist point - some evidence of benefit
• Psychological support: Acknowledge severity; screen for depression; consider counselling
• Hospital admission criteria: Unable to tolerate oral intake, >5% weight loss, ketonuria ≥3+, electrolyte abnormality, comorbidities

Pharmacological

• First-line antiemetics (RCOG GTG 69):
  • Cyclizine 50mg PO/IV/IM TDS
  • Prochlorperazine 5-10mg PO TDS or 12.5mg IM
  • Promethazine 25mg PO BD-TDS (sedating)
• Second-line: Ondansetron 4-8mg PO/IV BD-TDS (RCOG notes small increased risk of cleft palate in first trimester - discuss with patient)
• Third-line: Metoclopramide 10mg PO/IV TDS (max 5 days - risk of extrapyramidal side effects)
• Corticosteroids: Hydrocortisone 100mg IV BD then convert to prednisolone 40-50mg OD, tapering over 2-3 weeks - reserved for refractory cases not responding to antiemetics; avoid before 11 weeks if possible
• IV fluids: 0.9% NaCl with 20-40 mmol/L KCl; avoid dextrose-containing fluids initially
• Thiamine: 100mg TDS oral or IV - give BEFORE any dextrose-containing fluids to prevent Wernicke's
• Thromboprophylaxis: LMWH during admission if dehydrated/immobilised (RCOG guidance)

Surgical/Interventional

• Not applicable; rarely, total parenteral nutrition (TPN) or NG/NJ feeding may be needed for extreme refractory cases

Referral Criteria

• Unable to tolerate oral fluids - hospital admission
• Weight loss >5% or ketonuria ≥3+ - hospital assessment
• Neurological symptoms (confusion, ataxia) - emergency assessment for Wernicke's
• Significant psychological distress - perinatal mental health support
• Persistent symptoms beyond 20 weeks - specialist obstetric review

• Resolution: Symptoms resolve by 16-20 weeks in ~90% of cases
• Persistent symptoms: ~10% continue beyond 20 weeks; ~1-3% have symptoms throughout pregnancy
• Recurrence: ~50-80% recurrence risk in subsequent pregnancies
• Fetal outcomes: Generally good; slight increased risk of SGA and preterm birth with severe HG
• Maternal outcomes: Excellent with appropriate management; Wernicke's encephalopathy is preventable with thiamine
• Psychological: Significant long-term psychological impact in some women - PTSD-like symptoms, reluctance to have further pregnancies
• Rare complications: Mallory-Weiss tear, oesophageal rupture, central pontine myelinolysis (rapid sodium correction), splenic avulsion

PUQE Score (Pregnancy-Unique Quantification of Emesis)

Antiemetic Stepwise Approach

Key Facts

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance resulting in hyperglycaemia of variable severity with onset or first recognition during pregnancy. It is one of the most common medical complications of pregnancy and is associated with increased risks for both mother and baby.

Epidemiology

Prevalence is approximately 5-7% of UK pregnancies (higher in some populations - up to 15-20% in South Asian women). Incidence is rising, largely driven by increasing obesity and older maternal age. GDM is the most common metabolic complication of pregnancy.

Aetiology

Pregnancy is a diabetogenic state due to anti-insulin hormones:

• Human placental lactogen (hPL): Main contributor - increases maternal insulin resistance
• Progesterone, cortisol, prolactin, oestrogen: Additional insulin antagonism
• GDM occurs when pancreatic beta cells cannot compensate adequately for pregnancy-induced insulin resistance
• Pre-existing subclinical insulin resistance (obesity, family history, ethnicity) predisposes

Pathophysiology

Maternal Symptoms

• Often asymptomatic - detected on screening OGTT
• Polyuria, polydipsia (if significant hyperglycaemia)
• Recurrent infections (candidiasis, UTI)
• Increased risk of pre-eclampsia (~12% in GDM vs ~5% in general population)

Fetal/Neonatal Complications

• Macrosomia (birth weight >4kg or >90th centile): ~25% of GDM pregnancies
• Shoulder dystocia: Increased risk with macrosomia
• Neonatal hypoglycaemia: Fetal hyperinsulinism; check blood glucose within 2-4 hours of birth
• Neonatal jaundice: Polycythaemia → increased bilirubin
• Respiratory distress syndrome: Hyperinsulinism inhibits surfactant production
• Polyhydramnios: Fetal polyuria from hyperglycaemia
• Stillbirth: Increased risk with poorly controlled GDM

Red Flags

• Large-for-gestational-age fetus on USS
• Polyhydramnios
• Uncontrolled hyperglycaemia despite maximum oral therapy - start insulin urgently
• Ketonuria - screen for possible T1DM or T2DM presenting in pregnancy
• Reduced fetal movements - urgent assessment

Bedside

• Urine dipstick: Glycosuria (triggers OGTT if persistent) at antenatal visits
• Capillary blood glucose monitoring: Self-monitoring after diagnosis - fasting, 1-hour post-meal
• Blood pressure: Pre-eclampsia screening (increased risk in GDM)

Bloods

• 75g OGTT at 24-28 weeks (NICE NG3 criteria):
  • Fasting glucose ≥5.6 mmol/L = GDM
  • 2-hour glucose ≥7.8 mmol/L = GDM
  • Offer earlier OGTT (16-18 weeks) + repeat at 24-28 weeks if previous GDM
• HbA1c at booking: If ≥48 mmol/mol, suggests pre-existing diabetes
• Renal function, lipids: Baseline assessment
• FBC: Baseline

Imaging

• Growth scans: Serial USS at 28, 32, 36 weeks - estimated fetal weight, abdominal circumference (macrosomia monitoring)
• USS for polyhydramnios: Amniotic fluid index

Special Tests

• Continuous glucose monitoring (CGM): Considered if targets not achieved or hypoglycaemia on insulin
• Fetal surveillance: Increased monitoring - CTG, USS Doppler as clinically indicated

Non-pharmacological

• Dietary modification: First-line - low glycaemic index diet, regular meals, complex carbohydrates, reduce refined sugars
• Exercise: 30 minutes moderate activity daily (e.g., brisk walking)
• Self-monitoring of blood glucose: Fasting + 1-hour post-meal initially; 4-7 times per day
• Targets (NICE NG3): Fasting <5.3 mmol/L, 1h post-meal <7.8 mmol/L, 2h post-meal <6.4 mmol/L
• Trial of diet and exercise for 1-2 weeks before starting medication

Pharmacological

• Metformin (if targets not met with diet): 500mg OD with meals, titrate to max 2g/day in divided doses; reduces insulin resistance; crosses placenta but no evidence of fetal harm (MiG trial 2008)
• Insulin (if metformin insufficient or fasting >7.0 at diagnosis):
  • Rapid-acting with meals (insulin aspart or lispro) if post-prandial hyperglycaemia
  • Intermediate/long-acting (isophane or insulin detemir) if fasting hyperglycaemia
  • Often combined basal-bolus regimen; dose titrated individually
• Glibenclamide: Second-line alternative to insulin if metformin fails (not preferred - increased neonatal hypoglycaemia and macrosomia; limited use in UK practice)

Surgical/Interventional

• Timing of delivery: NICE NG3 recommends advising birth by 40+6 weeks for GDM on diet alone; 37+0 to 38+6 if on medication or with complications
• Induction of labour: Offered if GDM with complications, macrosomia, or at 40+6
• Caesarean section: Offered if estimated fetal weight >4.5kg or other obstetric indications

Referral Criteria

• All women with GDM - joint obstetric/diabetes team management
• Fasting glucose >7.0 at diagnosis - immediate insulin initiation
• Unable to achieve targets on maximum metformin - add insulin
• Evidence of fetal macrosomia or complications - increased obstetric surveillance

• Resolution: GDM resolves after delivery in the vast majority
• Postpartum T2DM: ~50% of women with GDM develop T2DM within 10-20 years; OGTT at 6-13 weeks postpartum then annual HbA1c screening (NICE NG3)
• Recurrence: GDM recurs in ~30-50% of subsequent pregnancies
• Maternal: Increased lifetime cardiovascular risk; increased risk of GDM → T2DM progression if overweight
• Neonatal: Good outcomes with well-managed GDM; macrosomia and hypoglycaemia are main short-term risks
• MiG trial (2008): Metformin non-inferior to insulin for maternal and neonatal outcomes
• Lifestyle modification: Postpartum diet and exercise reduce T2DM progression by ~50% (DPP trial data extrapolated)

NICE NG3 Risk Factors for GDM Screening

Blood Glucose Targets in GDM (NICE NG3)

GDM Management Stepwise Approach

Key Facts

Pre-eclampsia is a pregnancy-specific disorder with potentially devastating consequences for mother and baby. It is a leading cause of maternal and perinatal morbidity and mortality worldwide. The only definitive treatment is delivery, but optimising timing of delivery balances maternal safety against fetal prematurity.

Epidemiology

Pre-eclampsia affects approximately 2-5% of pregnancies worldwide and 2-3% in the UK. It is the leading direct cause of maternal death in the UK. Globally, it causes approximately 50,000-70,000 maternal deaths per year. Eclampsia occurs in approximately 0.5-1 per 1,000 deliveries in the UK. HELLP syndrome occurs in approximately 0.2-0.8% of all pregnancies.

Aetiology

Two-stage model:

Risk factors:

• High risk (≥1 = aspirin): Previous pre-eclampsia, CKD, autoimmune disease (SLE, APS), type 1/2 diabetes, chronic hypertension
• Moderate risk (≥2 = aspirin): Nulliparity, age ≥40, BMI ≥35, family history, multiple pregnancy, IVF, pregnancy interval >10 years

Pathophysiology

• Vascular: Vasoconstriction, hypertension

• Hepatic: Periportal necrosis, subcapsular haemorrhage → HELLP syndrome, hepatic rupture
• CNS: Cerebral oedema, vasospasm → eclampsia (seizures), PRES (posterior reversible encephalopathy syndrome)
• Haematological: Microangiopathic haemolysis, thrombocytopenia, DIC
• Placental: Growth restriction, abruption, stillbirth

Hypertension

• Systolic ≥140 or diastolic ≥90 mmHg (on 2 occasions at least 4h apart)
• Severe: ≥160/110 mmHg

Proteinuria

• Urine PCR ≥30 mg/mmol (equivalent to ≥300mg/24h)
• Dipstick ≥1+ (must confirm with PCR)

Symptoms of Severe Pre-eclampsia

• Severe headache (frontal, throbbing, not relieved by simple analgesia)
• Visual disturbance (blurred vision, flashing lights, scotomata)
• Epigastric/right upper quadrant pain (hepatic capsule distension)
• Sudden facial/hand oedema
• Nausea and vomiting
• Brisk reflexes, clonus (≥3 beats)

Eclampsia

• Tonic-clonic seizures in the context of pre-eclampsia
• Can occur antepartum (38%), intrapartum (18%), or postpartum (44%)

HELLP Syndrome

• Haemolysis (raised LDH, fragmented red cells, raised unconjugated bilirubin)
• Elevated liver enzymes (AST/ALT >70 IU/L)
• Low platelets (<100 × 10⁹/L)

Red Flags

• BP ≥160/110 - urgent antihypertensive treatment needed
• Symptoms of severe pre-eclampsia - admit, investigate, consider delivery
• Eclamptic seizure - magnesium sulfate, stabilise, plan delivery
• Platelets <50 or rapidly falling - HELLP, risk of DIC
• Pulmonary oedema, oliguria (<0.5ml/kg/h) - ICU involvement

Bedside

• Blood pressure: Validated automated device; manual if automated reading abnormal
• Urine dipstick: Proteinuria screening; confirm with uPCR if ≥1+
• Urine protein:creatinine ratio (uPCR): ≥30 mg/mmol = significant proteinuria
• Reflexes: Brisk reflexes, clonus (≥3 beats) - CNS hyperexcitability
• Fetal assessment: CTG, fetal movements

Bloods

• FBC: Thrombocytopenia (HELLP), haemoconcentration
• U&Es, creatinine, uric acid: AKI (creatinine >90 μmol/L), raised urate
• LFTs: AST/ALT elevation (HELLP, hepatic involvement)
• LDH: Elevated in haemolysis/HELLP
• Coagulation screen: DIC screening (PT, APTT, fibrinogen)
• Blood film: Fragmented red cells (schistocytes) in HELLP
• PlGF-based testing (NICE DG49): Placental growth factor - PlGF <100 pg/mL suggests pre-eclampsia; sFlt-1:PlGF ratio >38 is highly predictive

Imaging

• USS: Fetal growth assessment (SGA common), amniotic fluid volume, umbilical artery Doppler
• Liver USS: If severe RUQ pain - exclude subcapsular haematoma, hepatic rupture

Special Tests

• 24-hour urine protein: Historically used (≥300mg/24h) but uPCR now preferred (faster)
• CT head: If atypical neurological features, to exclude intracranial haemorrhage
• MRI brain: PRES (posterior reversible encephalopathy syndrome) if suspected

Non-pharmacological

• Admission: For severe pre-eclampsia, symptoms, or worsening parameters
• Monitoring: Frequent BP (at least 4-hourly; continuous if severe), daily bloods (FBC, LFTs, U&Es), uPCR, strict fluid balance
• Fetal monitoring: CTG, serial growth scans, umbilical artery Doppler

Pharmacological

• Antihypertensives (NICE NG133):
  • First-line: Labetalol 100mg BD, titrate to max 800mg/day in divided doses (avoid in asthma)
  • Second-line: Nifedipine MR 20mg BD, titrate to max 80mg/day
  • Third-line: Methyldopa 250mg BD-TDS (max 3g/day)
  • IV for severe HTN (≥160/110): IV labetalol 20mg bolus, then 40mg after 10 min, then 80mg (max 200mg total); or IV hydralazine 5mg bolus
• Magnesium sulfate (eclampsia prevention/treatment - MAGPIE trial):
  • Loading: 4g IV over 5-15 minutes
  • Maintenance: 1g/hour for 24 hours
  • Monitor: Respiratory rate (>12/min), urine output (>25ml/h), patellar reflexes (must be present)
  • Toxicity: Calcium gluconate 10ml 10% IV for magnesium toxicity
• Aspirin prophylaxis: 150mg nocte from 12 weeks to 36 weeks for at-risk women (ASPRE trial - 62% reduction in preterm pre-eclampsia)
• Corticosteroids: Betamethasone 12mg IM × 2 doses 24h apart if delivery anticipated <34+6 weeks (fetal lung maturity)

Surgical/Interventional

• Delivery (definitive treatment):
  • ≥37 weeks: Deliver (NICE NG133, supported by HYPITAT trial)
  • 34-37 weeks with severe features: Consider delivery after stabilisation and steroids
  • <34 weeks: Attempt to prolong pregnancy with close monitoring if condition allows; deliver if maternal or fetal deterioration
  • Mode: Vaginal delivery preferred if feasible; caesarean section if deteriorating, failed induction, or fetal compromise
• Postpartum: Continue antihypertensives; monitor BP for at least 6 weeks; review at 6-8 weeks

Referral Criteria

• New hypertension + proteinuria after 20 weeks - urgent obstetric review
• Severe pre-eclampsia or HELLP - consultant-led care, consider HDU/ITU
• Eclampsia - obstetric emergency; senior obstetric and anaesthetic input
• Previous pre-eclampsia - pre-conception counselling for subsequent pregnancies

• Maternal mortality: Pre-eclampsia/eclampsia accounts for ~5% of direct maternal deaths in the UK (MBRRACE-UK)
• HELLP syndrome mortality: ~1-3% (higher if complicated by hepatic rupture or DIC)
• Eclampsia mortality: ~1-2% in developed countries
• Recurrence: ~15-20% risk of pre-eclampsia in subsequent pregnancy (~25% if severe/early-onset)
• Fetal/neonatal: Growth restriction in ~25-30% of pre-eclamptic pregnancies; prematurity if early delivery required
• Long-term maternal risk: Women with pre-eclampsia have 2-4× increased lifetime risk of cardiovascular disease, chronic hypertension, stroke, and CKD
• Aspirin prophylaxis: ASPRE trial showed 62% reduction in preterm pre-eclampsia when aspirin 150mg given from 11-14 weeks
• MAGPIE trial: Magnesium sulfate reduced eclampsia risk by 58% in women with pre-eclampsia

Classification of Hypertensive Disorders in Pregnancy

Key Landmark Trials

Key Facts

Eclampsia is defined as the occurrence of one or more generalised tonic-clonic seizures in association with pre-eclampsia. It is a medical emergency with significant maternal and fetal mortality if not promptly managed.

Epidemiology

• Incidence: approximately 1 in 2,000 pregnancies in the UK
• UK maternal mortality from eclampsia/pre-eclampsia: approximately 0.3 per 100,000 maternities
• More common in primigravidae, multiple pregnancies, and extremes of maternal age
• Can occur antepartum (38%), intrapartum (18%), or postpartum (44%)

Aetiology

• Arises from severe pre-eclampsia with cerebral vasospasm and endothelial dysfunction
• Risk factors include: nulliparity, pre-existing hypertension, chronic kidney disease, autoimmune disease (SLE, antiphospholipid syndrome), diabetes, BMI >35, age >40, multiple pregnancy, family history of pre-eclampsia
• Abnormal placentation with defective spiral artery remodelling is the underlying pathological process

Pathophysiology

• Inadequate trophoblastic invasion of spiral arteries leads to placental ischaemia
• Release of anti-angiogenic factors (sFlt-1, soluble endoglin) causes widespread endothelial dysfunction
• Cerebral vasospasm and blood-brain barrier disruption lead to cerebral oedema and seizures
• Posterior reversible encephalopathy syndrome (PRES) is the radiological correlate on MRI

Typical Presentation

• Generalised tonic-clonic seizures in a pregnant or recently delivered woman
• Often preceded by symptoms of severe pre-eclampsia: severe headache, visual disturbance (blurred vision, scotomata, flashing lights), epigastric/right upper quadrant pain
• Hypertension (BP ≥140/90 mmHg) with proteinuria (≥300mg/24h or PCR ≥30mg/mmol)

Prodromal Symptoms

• Severe headache unresponsive to simple analgesia
• Visual disturbance (photopsia, scotomata, cortical blindness)
• Epigastric or right upper quadrant pain (hepatic capsule distension)
• Hyperreflexia and clonus (≥3 beats)
• Rapidly progressive oedema

Red Flags

• Seizures at any point in pregnancy or within 6 weeks postpartum
• Systolic BP >160 mmHg or diastolic >110 mmHg
• HELLP syndrome features (haemolysis, elevated liver enzymes, low platelets)
• Papilloedema
• Signs of placental abruption
• Oliguria (<0.5 mL/kg/hr)
• Glasgow Coma Scale <14

Bedside

• Blood pressure monitoring (every 15 minutes during acute phase)
• Urinalysis (proteinuria quantification - PCR or 24h collection)
• Continuous CTG for fetal monitoring
• Fluid balance chart (strict input/output)
• Capillary blood glucose

Bloods

• FBC (particularly platelet count - <100 × 10⁹/L suggests HELLP)
• U&Es (renal function - uric acid, creatinine)
• LFTs (ALT/AST elevation suggests HELLP)
• Coagulation screen (DIC screen)
• Blood film (for fragmented red cells/schistocytes)
• Group and save / crossmatch
• Serum magnesium levels (therapeutic range 2-4 mmol/L)

Imaging

• CT head if atypical features or prolonged post-ictal state
• MRI brain if suspecting PRES or other intracranial pathology
• Ultrasound for fetal assessment (growth, liquor volume, Dopplers)

Special Tests

• PlGF-based testing if <37 weeks (NICE NG133)
• Urine protein:creatinine ratio
• Arterial blood gas if respiratory compromise

Non-pharmacological

• Multidisciplinary approach: obstetrics, anaesthetics, midwifery, neonatology
• Left lateral position during seizure
• Airway management and high-flow oxygen
• Monitor in high-dependency setting
• Strict fluid balance (limit IV fluids to 80 mL/hr to reduce pulmonary oedema risk)

Pharmacological

• Magnesium sulphate: 4g IV loading dose over 5-15 minutes, followed by 1g/hr infusion for 24 hours (MAGPIE trial evidence)
• Recurrent seizures: further 2g IV magnesium sulphate bolus
• Antihypertensives: Labetalol 200mg PO or 50mg IV (first-line per NICE NG133); nifedipine 10-20mg PO (second-line); hydralazine 5mg IV (third-line)
• Target BP <150/100 mmHg
• Antidote for magnesium toxicity: calcium gluconate 10% 10 mL IV over 10 minutes

Surgical/Interventional

• Delivery is the definitive treatment
• If ≥34 weeks: plan delivery within 24-48 hours
• If <34 weeks: consider corticosteroids (betamethasone 12mg IM × 2 doses, 24h apart) for fetal lung maturation if delivery can be safely delayed
• Emergency caesarean section if maternal or fetal compromise

Referral Criteria

• All cases require consultant obstetrician and anaesthetist involvement
• HDU/ITU admission for ventilatory support or multi-organ failure
• Follow-up at 6-8 weeks postpartum with BP and proteinuria check
• Referral to specialist hypertension clinic if persistent hypertension

• UK maternal mortality from eclampsia: approximately 1-2% (has fallen with improved management)
• Perinatal mortality: 5-12% (higher with preterm delivery)
• 35% of women develop complications: HELLP syndrome, DIC, renal failure, pulmonary oedema, ARDS
• Risk of recurrence in subsequent pregnancy: 2-5% for eclampsia, 15-25% for pre-eclampsia
• Long-term cardiovascular risk is increased: 2-4× risk of chronic hypertension, 2× risk of ischaemic heart disease
• Aspirin 75-150mg from 12 weeks in subsequent pregnancies reduces pre-eclampsia risk by 17% (NICE NG133)

MAGPIE Trial Summary

Severity Classification

Magnesium Sulphate Monitoring

Key Facts

HELLP syndrome is a serious complication of pregnancy characterised by haemolysis, elevated liver enzymes, and low platelet count. It is considered a severe variant of pre-eclampsia, though it may present independently.

Epidemiology

• Incidence: 0.5-0.9% of all pregnancies
• Complicates 10-20% of pregnancies with severe pre-eclampsia
• Peak incidence between 27-37 weeks gestation
• 30% of cases present postpartum (usually within 48 hours)
• More common in multiparous women and those >25 years of age

Aetiology

• Shares common pathophysiology with pre-eclampsia: abnormal placentation and endothelial dysfunction
• Risk factors overlap with pre-eclampsia: previous HELLP/pre-eclampsia, nulliparity, age >40, multiple pregnancy, BMI >35, chronic hypertension, autoimmune conditions
• Recurrence rate: 2-19% in subsequent pregnancies

Pathophysiology

• Abnormal trophoblastic invasion leads to placental ischaemia
• Release of inflammatory mediators causes widespread endothelial activation
• Haemolysis: microangiopathic haemolytic anaemia (MAHA) due to endothelial damage and fibrin deposition in microvasculature
• Elevated liver enzymes: periportal and focal hepatic necrosis with hepatic sinusoidal obstruction
• Low platelets: increased consumption due to endothelial damage and DIC
• Hepatic complications can progress to subcapsular haematoma or hepatic rupture

Typical Presentation

• Right upper quadrant or epigastric pain (65-86% of cases)
• Nausea and vomiting (36-50%)
• Malaise and fatigue
• May present with pre-eclamptic features: hypertension, proteinuria, oedema

Atypical Presentations

• Up to 15-20% present without hypertension or proteinuria
• Can mimic acute fatty liver of pregnancy, cholecystitis, hepatitis, or gastroenteritis
• Shoulder tip pain may indicate hepatic capsule distension or diaphragmatic irritation

Red Flags

• Rapidly falling platelet count (<50 × 10⁹/L)
• Rising LDH and falling haptoglobin (progressive haemolysis)
• Epigastric/RUQ pain with shoulder tip pain (hepatic subcapsular haematoma)
• Signs of DIC: widespread bleeding, petechiae, ecchymoses
• Severe hypertension (>160/110 mmHg)
• Visual disturbance, headache, seizures (eclampsia)
• Oliguria or anuria

Bedside

• Blood pressure monitoring
• Urinalysis (proteinuria)
• CTG for continuous fetal monitoring
• Fluid balance chart

Bloods

• FBC: platelet count (<150 × 10⁹/L confirms low platelets)
• Blood film: schistocytes, fragmented red cells (evidence of MAHA)
• LFTs: AST/ALT elevated (≥70 IU/L), raised bilirubin
• LDH: elevated (>600 IU/L indicates haemolysis)
• Haptoglobin: low or absent (consumed in haemolysis)
• Coagulation screen: PT, APTT, fibrinogen (DIC screen)
• D-dimer: elevated in DIC
• U&Es: creatinine, uric acid (renal involvement)
• Group and save / crossmatch: prepare for transfusion

Imaging

• Liver ultrasound: assess for subcapsular haematoma, hepatic infarction
• CT abdomen if suspecting hepatic rupture
• Obstetric ultrasound: fetal growth, liquor volume, umbilical artery Dopplers

Special Tests

• ADAMTS13 if TTP suspected
• Antiphospholipid antibodies if indicated

Non-pharmacological

• Multidisciplinary management: obstetrics, haematology, anaesthetics, hepatology
• High-dependency or intensive care monitoring
• Strict fluid balance
• Crossmatch and prepare blood products

Pharmacological

• Antihypertensives: labetalol (first-line), nifedipine, or hydralazine as per NICE NG133
• Magnesium sulphate: seizure prophylaxis (4g IV loading, 1g/hr maintenance)
• Corticosteroids for fetal lung maturity: betamethasone 12mg IM × 2 doses (24h apart) if <34 weeks
• Dexamethasone for maternal benefit (to improve platelet count): evidence is limited; some centres use 10mg IV 12-hourly
• Blood product replacement: platelets if <50 × 10⁹/L or actively bleeding; FFP/cryoprecipitate if DIC
• Tranexamic acid 1g IV if significant haemorrhage

Surgical/Interventional

• Delivery is the definitive treatment
• ≥34 weeks: deliver within 24-48 hours
• <34 weeks: stabilise, administer steroids, deliver if maternal condition deteriorates
• Mode of delivery: vaginal delivery may be attempted if cervix favourable; caesarean section if urgent
• If hepatic rupture: emergency laparotomy with hepatic packing

Referral Criteria

• Consultant obstetrician and anaesthetist involvement mandatory
• Haematology input for DIC management
• Hepatology/surgical input if hepatic complications
• Follow-up at 6-8 weeks postpartum with blood tests

• Maternal mortality: 1-3% (higher in developing countries)
• Perinatal mortality: 7-20% (largely dependent on gestational age at delivery)
• Complications: DIC (20%), placental abruption (16%), acute renal failure (7%), pulmonary oedema (6%), hepatic rupture (1-2%)
• Most haematological and hepatic abnormalities resolve within 48-72 hours postpartum
• Platelet nadir typically at 24-48 hours postpartum
• Recurrence risk in subsequent pregnancies: 2-19%
• Long-term: increased risk of chronic hypertension and cardiovascular disease

Mississippi Classification

Tennessee Diagnostic Criteria

Differential: HELLP vs AFLP

Key Facts

Antepartum haemorrhage is any bleeding from the genital tract from 24+0 weeks of pregnancy until delivery. It is a common obstetric emergency requiring systematic assessment to determine the cause, severity, and appropriate management.

Epidemiology

• Complicates 3-5% of pregnancies
• Accounts for significant proportion of obstetric emergencies
• Placenta praevia: 0.5% of pregnancies at term
• Placental abruption: 1% of pregnancies
• Unexplained APH: approximately 50% of cases

Aetiology

• Placenta praevia (low-lying placenta covering or near the cervical os)
• Placental abruption (premature separation of normally sited placenta)
• Vasa praevia (fetal vessels crossing the cervical os - rare but high fetal mortality)
• Marginal bleeding (bleeding from placental edge)
• Cervical causes: cervical ectropion, cervical cancer, cervical polyp
• Infection: cervicitis, vaginitis
• Unexplained (most common overall)

Pathophysiology

• Placenta praevia: placental implantation in lower uterine segment; bleeding occurs as lower segment develops
• Abruption: premature separation due to haemorrhage into the decidua basalis; may be concealed or revealed
• Vasa praevia: rupture of unprotected fetal vessels, typically at membrane rupture

Placenta Praevia Presentation

• Painless bright red vaginal bleeding (classically recurrent)
• Soft, non-tender uterus
• Malpresentation common (breech, transverse lie)
• Usually no fetal compromise unless massive bleeding

Placental Abruption Presentation

• Constant abdominal pain with or without vaginal bleeding
• Woody hard, tender uterus on palpation
• Degree of shock may be disproportionate to visible blood loss (concealed haemorrhage)
• Fetal distress or intrauterine fetal death

Vasa Praevia Presentation

• Painless vaginal bleeding at membrane rupture
• Rapid fetal compromise (sinusoidal CTG pattern)
• Fetal mortality >50% if not diagnosed antenatally

Red Flags

• Haemodynamic instability (tachycardia, hypotension)
• Woody hard uterus (abruption)
• Abnormal CTG
• Bleeding at membrane rupture (vasa praevia)
• Large volume blood loss (>500 mL)
• Coagulopathy

Bedside

• ABCDE assessment and haemodynamic monitoring
• CTG (continuous fetal monitoring)
• Speculum examination (DO NOT perform digital VE until praevia excluded)
• Weigh pads/estimate blood loss
• Group and save / crossmatch urgently

Bloods

• FBC (haemoglobin, platelet count)
• Coagulation screen (PT, APTT, fibrinogen)
• Group and crossmatch (minimum 4 units in massive haemorrhage)
• Kleihauer test (all RhD-negative women - quantifies fetomaternal haemorrhage)
• U&Es, LFTs

Imaging

• Transabdominal ultrasound: placental localisation, fetal assessment
• Transvaginal ultrasound: gold standard for placental localisation (safe even with praevia)
• Doppler assessment of fetal wellbeing

Special Tests

• Apt test or haemoglobin electrophoresis if suspecting fetal blood (vasa praevia)
• Fibronectin or cervical length if preterm labour suspected

Non-pharmacological

• ABCDE approach with simultaneous resuscitation
• Two large-bore IV cannulae (14-16G)
• Activate massive obstetric haemorrhage protocol if appropriate
• Senior obstetric and anaesthetic involvement
• Neonatal team alert

Pharmacological

• Anti-D immunoglobulin: 500 IU IM minimum to all RhD-negative women; Kleihauer to guide additional doses
• Antenatal corticosteroids: betamethasone 12mg IM × 2 (24h apart) if 24-34+6 weeks
• Tocolysis: may be considered if preterm labour with mild APH (nifedipine 20mg PO); contraindicated with significant abruption
• IV fluid resuscitation and blood product replacement as needed
• Tranexamic acid 1g IV in massive haemorrhage

Surgical/Interventional

• Placenta praevia: elective caesarean section at 36-37 weeks (RCOG GTG 27a)
• Major abruption: emergency delivery (usually caesarean section) if fetal compromise
• Vasa praevia: elective caesarean section at 34-36 weeks if diagnosed antenatally
• Uterine compression sutures (B-Lynch), balloon tamponade, or uterine artery embolisation for ongoing haemorrhage

Referral Criteria

• All APH requires hospital assessment
• Consultant obstetrician review for any significant APH
• Haematology input for coagulopathy
• Blood bank alert for massive haemorrhage

• Perinatal mortality varies by cause: placenta praevia (~1-2%), abruption (up to 30% in severe cases), vasa praevia (>50% if undiagnosed)
• Maternal mortality rare in developed countries but remains significant worldwide
• Recurrence risk: placenta praevia 4-8%, abruption 6-17%
• APH associated with increased risk of preterm delivery, FGR, and neonatal morbidity
• Women with unexplained APH have 2× risk of preterm delivery and 1.5× risk of low birth weight

RCOG APH Severity Classification

Causes by Frequency

Key Facts

Placenta praevia is defined as a placenta that lies wholly or partially in the lower uterine segment, covering or reaching the internal cervical os. It is an important cause of antepartum haemorrhage and necessitates planned delivery by caesarean section.

Epidemiology

• Low-lying placenta at 20-week anomaly scan: 5-10%
• Placenta praevia at term: 0.5% (most migrate as lower segment forms)
• Incidence increasing due to rising caesarean section rates
• Previous CS increases risk: 1 CS = 0.65%, 2 CS = 1.5%, 3 CS = 2.2%, ≥4 CS = 10%

Aetiology

• Previous caesarean section (strongest risk factor)
• Previous uterine surgery (myomectomy, curettage)
• Multiparity
• Advanced maternal age (>40 years)
• Multiple pregnancy
• Assisted reproduction (IVF/ICSI)
• Smoking
• Previous placenta praevia (recurrence rate 4-8%)

Pathophysiology

• Placenta implants in the lower uterine segment rather than the fundus
• As the lower segment develops and thins in the third trimester, the placenta separates from the uterine wall, causing haemorrhage
• The lower segment cannot contract effectively to control bleeding (unlike the upper segment)
• Placenta accreta spectrum may develop where the placenta abnormally invades the myometrium

Typical Presentation

• Painless bright red vaginal bleeding (classically recurrent episodes of increasing severity)
• First episode usually occurs in late second or third trimester
• Soft, non-tender, relaxed uterus
• Malpresentation common: breech (15%), transverse lie (15%), unstable lie
• High presenting part / non-engaged head at term

Incidental Finding

• Many cases now diagnosed at 20-week anomaly scan before symptoms
• Repeat scan at 32 weeks to assess placental migration
• Further scan at 36 weeks to plan mode of delivery

Red Flags

• Major haemorrhage with haemodynamic compromise
• Signs of concealed bleeding (tachycardia, hypotension despite minimal visible loss)
• Confirmed praevia with contractions (risk of massive haemorrhage)
• Symptoms suggesting placenta accreta (painless haematuria, bladder symptoms)

Bedside

• ABCDE assessment if active bleeding
• Speculum examination only (NO digital VE)
• CTG for fetal monitoring
• Blood pressure and pulse monitoring

Bloods

• FBC, group and save (crossmatch if bleeding)
• Coagulation screen
• Kleihauer test (RhD-negative women)
• U&Es

Imaging

• Transvaginal ultrasound (TVS): gold standard for diagnosis - measures distance from placental edge to internal os
• Transabdominal ultrasound: screening tool at anomaly scan
• MRI: may be useful to assess placenta accreta spectrum (particularly posterior placenta)
• Colour Doppler: assess for placental invasion/accreta and vasa praevia

Special Tests

• If placenta accreta suspected: MRI pelvis, multidisciplinary planning
• Serial ultrasound for growth and Dopplers if recurrent bleeds

Non-pharmacological

• If asymptomatic: outpatient management if no bleeding episodes and lives close to hospital
• If symptomatic: inpatient admission after any significant bleed
• Avoid intercourse, strenuous activity
• Patient education regarding when to attend hospital
• Ensure blood group known and antibodies checked

Pharmacological

• Anti-D immunoglobulin for RhD-negative women after any bleeding episode
• Antenatal corticosteroids: betamethasone 12mg IM × 2 if preterm delivery anticipated
• Iron supplementation if anaemic (ferrous sulphate 200mg TDS)
• Tocolysis: may be considered for acute tocolysis (nifedipine) to allow steroid administration

Surgical/Interventional

• Elective caesarean section at 36-37 weeks for confirmed placenta praevia (RCOG GTG 27a)
• Performed by experienced consultant obstetrician
• If placenta accreta suspected: planned delivery in specialist centre with interventional radiology, cell salvage, and senior surgical team
• Emergency CS at any gestation if life-threatening haemorrhage
• B-Lynch suture, uterine artery ligation, internal iliac artery ligation, or peripartum hysterectomy for uncontrolled haemorrhage

Referral Criteria

• Placenta praevia confirmed at 32-week scan: refer to consultant-led unit
• Suspected placenta accreta: refer to specialist centre (regional fetal medicine unit)
• Any bleeding episode: immediate hospital assessment

• Most low-lying placentas at 20 weeks will migrate by term (>90%)
• Anterior placenta praevia with previous CS scar: higher risk of accreta spectrum
• Maternal mortality: rare in UK (<1 per 100,000 with praevia alone)
• Perinatal mortality: approximately 1-2% (mainly from prematurity)
• Risk of massive haemorrhage requiring hysterectomy: 5-8% for praevia, up to 40% for accreta
• Recurrence rate: 4-8% in subsequent pregnancies

Classification

Placenta Accreta Spectrum

Risk of Accreta by CS Number with Praevia

Key Facts

Placental abruption is the premature separation of a normally implanted placenta from the uterine wall before delivery of the fetus. It is a major cause of antepartum haemorrhage and is associated with significant maternal and perinatal morbidity and mortality.

Epidemiology

• Incidence: approximately 1% of all pregnancies
• Responsible for 30% of cases of APH
• Leading cause of antepartum stillbirth in the UK
• More common in the third trimester but can occur from 20 weeks

Aetiology

• Pre-eclampsia/hypertension (strongest association)
• Previous placental abruption (recurrence risk 6-17%)
• Cigarette smoking (dose-dependent, 2× risk)
• Cocaine use (5× risk)
• Abdominal trauma (RTC, domestic violence)
• Preterm premature rupture of membranes
• Multiple pregnancy
• Polyhydramnios (sudden decompression)
• Thrombophilia (antiphospholipid syndrome, factor V Leiden)
• Advanced maternal age, high parity

Pathophysiology

• Rupture of maternal decidual spiral arteries causes bleeding into the decidua basalis
• Blood tracks between the placenta and uterine wall, causing separation
• Revealed haemorrhage: blood tracks down to cervical os and is visible
• Concealed haemorrhage: blood is trapped behind the placenta with no vaginal loss (more dangerous)
• Couvelaire uterus: severe extravasation of blood into the myometrium causing a blue/purple discolouration

Typical Presentation

• Constant abdominal pain (unlike the intermittent pain of contractions)
• Vaginal bleeding (may be absent in concealed abruption)
• Woody hard, tender uterus on palpation
• Uterine irritability with high-frequency contractions
• Signs of maternal shock (tachycardia, hypotension) - may be disproportionate to visible blood loss

Classification by Severity

• Mild: small revealed bleed, minimal pain, no fetal compromise
• Moderate: moderate bleeding and pain, some fetal compromise
• Severe: massive haemorrhage, coagulopathy, fetal death

Red Flags

• Concealed haemorrhage (shock without proportionate vaginal bleeding)
• Fetal bradycardia or absent heart sounds
• DIC (widespread oozing, petechiae)
• Couvelaire uterus
• Oliguria/anuria
• Rapidly increasing uterine size (concealed blood accumulation)

Bedside

• ABCDE assessment
• Continuous CTG (pathological trace with abruption: late decelerations, reduced variability, sinusoidal pattern)
• Blood pressure, pulse (every 15 minutes)
• Fluid balance chart
• Speculum examination (do not perform digital VE until praevia excluded)

Bloods

• FBC (urgent haemoglobin and platelet count)
• Coagulation screen: PT, APTT, fibrinogen (fibrinogen <2 g/L is concerning; <1 g/L indicates severe DIC)
• Crossmatch (minimum 4-6 units in severe cases)
• Kleihauer test (RhD-negative women)
• U&Es (renal function)
• LFTs (if pre-eclampsia suspected)

Imaging

• Ultrasound: may show retroplacental clot but USS has poor sensitivity for abruption (negative scan does not exclude it)
• Diagnosis is primarily clinical

Special Tests

• Thrombophilia screen after acute episode resolves (if recurrent abruption)
• Placental histology postpartum

Non-pharmacological

• ABCDE approach with aggressive resuscitation
• Two large-bore IV cannulae (14-16G)
• Activate major obstetric haemorrhage protocol if severe
• Left lateral position
• Continuous CTG
• Senior obstetric and anaesthetic involvement

Pharmacological

• IV fluid resuscitation: crystalloid initially, then blood products
• Blood products: packed red cells, FFP, platelets, cryoprecipitate as guided by coagulation results (target fibrinogen >2 g/L)
• Anti-D immunoglobulin for RhD-negative women
• Antenatal corticosteroids if <34+6 weeks and delivery can be delayed safely
• Tranexamic acid 1g IV in major haemorrhage
• DO NOT delay delivery for corticosteroids if maternal or fetal compromise

Surgical/Interventional

• Mild abruption at term: induce labour with artificial ROM and oxytocin if CTG reassuring
• Moderate-severe abruption: emergency caesarean section (category 1)
• Intrauterine fetal death: aim for vaginal delivery if maternal condition allows; ensure coagulopathy corrected
• Postpartum: active management of third stage, uterotonic agents
• B-Lynch suture, balloon tamponade, or hysterectomy for refractory PPH

Referral Criteria

• All suspected abruptions require immediate hospital assessment
• Consultant obstetrician must be informed
• Haematology input for DIC
• Subsequent pregnancy: consultant-led care, serial growth scans

• Perinatal mortality: 15-30% overall; up to 50% in severe cases
• Maternal mortality: <1% in developed countries
• DIC complicates 10-30% of significant abruptions
• Renal failure: 1-3% of severe cases
• Recurrence risk: 6-17% after one abruption; 25% after two
• Associated with long-term increased cardiovascular risk in the mother
• Surviving neonates at risk of prematurity-related morbidity

Abruption Severity Classification

DIC Management Targets

Key Facts

Preterm labour is defined as the onset of regular painful uterine contractions leading to progressive cervical dilatation between 24+0 and 36+6 weeks of gestation. Preterm birth remains the leading cause of neonatal mortality and long-term disability.

Epidemiology

• 7-8% of births in the UK are preterm
• Approximately 60,000 preterm births per year in the UK
• Spontaneous preterm labour accounts for 70-80% of preterm births
• Iatrogenic preterm delivery (for maternal/fetal indication) accounts for 20-30%
• Incidence has been relatively stable or slightly increasing due to assisted reproduction

Aetiology

• Infection/inflammation (most common identifiable cause): chorioamnionitis, bacterial vaginosis, UTI
• Cervical insufficiency
• Uterine abnormalities (bicornuate uterus, fibroids)
• Multiple pregnancy
• Polyhydramnios
• Previous preterm birth (strongest risk factor: recurrence risk 15-50%)
• PPROM
• Placental abruption
• Social factors: smoking, low socioeconomic status, stress, domestic violence

Pathophysiology

• Multiple pathways converge on activation of the myometrium and cervical ripening

• Premature activation of the hypothalamic-pituitary-adrenal axis
• Cervical shortening and funnelling precede clinical labour
• Decidual haemorrhage/abruption activates thrombin which stimulates contractions

Symptoms

• Regular, painful uterine contractions (≥4 in 20 minutes)
• Lower abdominal cramping or pelvic pressure
• Low back pain (constant or rhythmic)
• Vaginal discharge (mucoid, bloody show)
• Sensation of pelvic pressure or heaviness

Signs

• Palpable regular uterine contractions on tocometry
• Cervical dilatation and/or effacement on examination
• Short cervical length on transvaginal ultrasound (<25mm is significant)

Red Flags

• Cervical dilatation >3cm (advanced preterm labour - tocolysis unlikely to be effective)
• Signs of chorioamnionitis (fever, tachycardia, uterine tenderness, offensive discharge)
• Vaginal bleeding (abruption)
• Abnormal CTG (fetal compromise)
• PPROM (pooling of liquor on speculum)

Bedside

• CTG (fetal monitoring)
• Speculum examination (look for cervical dilatation, pooling of liquor, bleeding)
• Fetal fibronectin (fFN) swab (if cervix <3cm dilated): negative result has >95% NPV for delivery within 7 days
• Urinalysis and urine MC&S
• Vital signs including temperature

Bloods

• FBC, CRP (infection screen)
• Blood cultures if pyrexial
• Group and save
• U&Es

Imaging

• Transvaginal cervical length measurement: <25mm is significant, <15mm is high risk
• Ultrasound for fetal presentation, weight estimation, liquor volume

Special Tests

• High vaginal swab and low vaginal swab for Group B Streptococcus
• Consider amniocentesis if infection suspected (rarely performed in UK practice)

Non-pharmacological

• Admit to unit with appropriate neonatal facilities
• In utero transfer to tertiary unit if <27 weeks gestation
• Neonatal team counselling regarding prognosis at given gestation
• Bed rest (limited evidence but commonly advised)

Pharmacological

• Antenatal corticosteroids: betamethasone 12mg IM × 2 doses (24 hours apart) if 24-34+6 weeks (NICE NG25). Single rescue course may be considered.
• Tocolysis: nifedipine 20mg PO stat then 10-20mg TDS-QDS (first-line, NICE NG25). Used to gain 48 hours for steroid effect and in utero transfer.
• Alternative tocolytic: atosiban (oxytocin receptor antagonist) 6.75mg IV bolus then infusion
• Magnesium sulphate for neuroprotection: 4g IV loading dose over 15 minutes if delivery expected within 24 hours at <30 weeks (reduces risk of cerebral palsy by 30%)
• Antibiotics: if evidence of infection (IV benzylpenicillin 3g then 1.5g 4-hourly for GBS prophylaxis)
• Erythromycin 250mg QDS PO for 10 days if PPROM (ORACLE trial)

Surgical/Interventional

• Cervical cerclage: rescue cerclage if cervical dilatation 1-4cm before 24 weeks with no infection (limited evidence)
• Prophylactic cerclage at 12-14 weeks for women with history of ≥3 preterm births or second-trimester losses
• Arabin pessary: alternative to cerclage (evidence debated)

Referral Criteria

• All women in suspected preterm labour require hospital assessment
• In utero transfer to tertiary unit if <27 weeks or anticipated neonatal surgical needs
• Preterm birth prevention clinic referral for women with risk factors in subsequent pregnancies

• Survival by gestational age: 24 weeks ~50%, 26 weeks ~75%, 28 weeks ~90%, 32 weeks ~95%, 34 weeks ~98%
• Major morbidity (cerebral palsy, chronic lung disease, severe disability): 24 weeks ~30%, 28 weeks ~10%, 32 weeks ~3%
• Antenatal corticosteroids reduce RDS by 34%, IVH by 46%, and neonatal death by 31%
• Magnesium sulphate reduces cerebral palsy by 30% when given before 30 weeks
• Recurrence risk of preterm birth: 15-50% (strongest predictor of subsequent preterm birth)

Survival and Outcome by Gestational Age

Key Trials

Key Facts

Premature rupture of membranes (PROM) refers to rupture of the fetal membranes prior to the onset of labour. When this occurs before 37 weeks, it is termed preterm PROM (PPROM). It is a significant cause of preterm birth and is associated with infectious complications.

Epidemiology

• PROM at term: occurs in approximately 8-10% of pregnancies
• PPROM: complicates 2-3% of pregnancies
• PPROM is responsible for 30-40% of all preterm births
• Most women with PROM at term will labour spontaneously within 24 hours (>60%)

Aetiology

• Infection (chorioamnionitis, bacterial vaginosis, GBS colonisation)
• Previous PPROM (recurrence risk 16-32%)
• Smoking
• Previous cervical surgery (cone biopsy, LLETZ)
• Uterine overdistension (polyhydramnios, multiple pregnancy)
• Cervical insufficiency
• Amniocentesis (1% risk)
• Low socioeconomic status, poor nutrition

Pathophysiology

• Weakening of the chorioamniotic membranes through enzymatic degradation (matrix metalloproteinases)
• Infection causes neutrophil infiltration and release of proteolytic enzymes
• Mechanical stress from uterine contractions or overdistension
• Programmed cell death and collagen remodelling contribute in term PROM

Typical Presentation

• Sudden gush of clear fluid from the vagina
• Continuous trickle or leaking of fluid
• Wet underwear or sanitary pad
• Fluid may be clear, straw-coloured, or blood-tinged

Signs on Examination

• Pooling of liquor in the posterior vaginal fornix on speculum examination
• Reduced liquor volume on ultrasound
• Positive bedside tests (nitrazine test, ferning, IGFBP-1, PAMG-1)

Red Flags

• Maternal pyrexia (>38°C) suggesting chorioamnionitis
• Maternal tachycardia (>100 bpm)
• Uterine tenderness
• Offensive vaginal discharge
• Fetal tachycardia (>160 bpm)
• Raised CRP or WCC
• Cord prolapse (especially with high presenting part)

Bedside

• Sterile speculum examination: look for pooling of liquor in posterior fornix
• IGFBP-1 or PAMG-1 test (Actim PROM / PartoSure): bedside immunoassay with high sensitivity and specificity
• Nitrazine test (pH >6.5 suggests amniotic fluid - less specific)
• Temperature, pulse, blood pressure
• CTG for fetal monitoring

Bloods

• FBC (WCC as baseline)
• CRP (baseline and twice weekly)
• Group and save
• Blood cultures if pyrexial

Imaging

• Ultrasound: assess liquor volume (oligohydramnios supports diagnosis), fetal presentation, growth

Special Tests

• High vaginal swab and low vaginal swab (including GBS culture)
• Urine MC&S
• Avoid digital VE unless in established labour (increases infection risk)

Non-pharmacological

• PROM at term (≥37 weeks): offer induction of labour (NICE NG25 recommends within 24 hours); or expectant management with 4-hourly observations for up to 24 hours if woman prefers
• PPROM (24-36+6 weeks): expectant management with close monitoring
• Regular observations: temperature and pulse 4-hourly, FBC and CRP twice weekly
• Avoid digital VE until in established labour

Pharmacological

• Erythromycin 250mg QDS PO for 10 days (or until labour, whichever sooner) - ORACLE trial evidence
• Do NOT use co-amoxiclav (increased NEC risk - ORACLE trial)
• Antenatal corticosteroids: betamethasone 12mg IM × 2 if 24-34+6 weeks
• Magnesium sulphate: 4g IV if delivery expected within 24 hours at <30 weeks (neuroprotection)
• GBS prophylaxis: IV benzylpenicillin 3g then 1.5g 4-hourly in labour if GBS positive or unknown

Surgical/Interventional

• Induction of labour at 37 weeks if PPROM has been managed expectantly
• Earlier delivery if signs of chorioamnionitis, fetal compromise, or significant abruption
• Mode of delivery guided by fetal presentation and condition

Referral Criteria

• All women with suspected PPROM require hospital assessment
• In utero transfer to tertiary unit if <27 weeks
• Neonatal counselling at extreme prematurity

• PROM at term: >90% will labour within 24 hours; 95% within 72 hours
• PPROM: 50% will deliver within 1 week; latency inversely proportional to gestational age
• Chorioamnionitis rate: 15-25% with PPROM
• Cord prolapse risk: 1-2% (higher with malpresentation)
• Neonatal sepsis: 2-5%
• Pulmonary hypoplasia risk: significant if PPROM <24 weeks with severe oligohydramnios
• Recurrence risk: 16-32%
• Perinatal mortality with PPROM: depends on gestational age and complications

ORACLE Trial Summary

Chorioamnionitis Diagnostic Criteria

Key Facts

Normal labour is the process by which the fetus, placenta, and membranes are expelled through the birth canal. It involves regular, progressive uterine contractions leading to cervical effacement and dilatation, descent and delivery of the fetus, and expulsion of the placenta.

Epidemiology

• Approximately 700,000 births per year in the UK
• Spontaneous vaginal delivery rate: approximately 52-58%
• Mean duration of first labour: 8-12 hours (nulliparous), 4-6 hours (multiparous)
• Mean gestation at spontaneous onset: 40 weeks

Aetiology

• Onset triggered by complex interplay of maternal and fetal factors
• Fetal hypothalamic-pituitary-adrenal axis activation increases cortisol production
• Progesterone withdrawal (functional rather than absolute in humans)
• Increased prostaglandin production from the decidua and membranes
• Oxytocin receptor upregulation in the myometrium
• Inflammatory cascade activation

Pathophysiology

• Cervical ripening: collagen degradation, increased hyaluronic acid, water content
• Myometrial contractions become coordinated through gap junction formation
• Fundal dominance: contractions strongest at fundus, propagating downwards
• Cardinal movements of labour: engagement, descent, flexion, internal rotation, extension, restitution, external rotation, expulsion

First Stage of Labour

• Latent phase (0-4cm): irregular contractions, slow cervical change, may last many hours
• Active phase (4-10cm): regular painful contractions (3-4 in 10 minutes), progressive dilatation ≥0.5cm/hr
• Show (mucoid blood-stained discharge)
• Spontaneous rupture of membranes may occur

Second Stage of Labour

• Full dilatation to delivery of baby
• Passive second stage: full dilatation without involuntary expulsive efforts
• Active second stage: expulsive contractions with maternal pushing
• Urge to push, rectal pressure, perineal stretching

Third Stage of Labour

• Delivery of placenta and membranes
• Active management (recommended): oxytocin, controlled cord traction (reduces PPH risk)
• Physiological management: no oxytocin, awaiting signs of separation

Red Flags During Labour

• Meconium-stained liquor (particularly thick/particulate)
• Pathological CTG (requires immediate action)
• Prolonged second stage
• Fresh vaginal bleeding not consistent with show
• Maternal pyrexia (>38°C)
• Cord prolapse

Bedside

• Intermittent auscultation (IA) with Pinard stethoscope or Doppler: every 15 min in first stage, every 5 min in second stage
• CTG only if risk factors present (meconium, oxytocin use, epidural, previous CS, abnormal IA)
• Vaginal examination (4-hourly in active first stage)
• Partogram documentation
• Temperature, pulse, BP hourly
• Urinalysis (ketones, protein)

Bloods

• Not routinely required in normal labour
• Group and save available
• FBC if excessive bleeding or planned instrumental delivery

Imaging

• Ultrasound for fetal position if uncertain (occipitoposterior vs anterior)

Special Tests

• Fetal blood sampling (FBS) if pathological CTG: pH >7.25 normal, 7.20-7.25 borderline, <7.20 abnormal
• Lactate on FBS: >4.8 mmol/L abnormal

Non-pharmacological

• Birth environment: low-risk women offered choice of birth setting (home, midwifery unit, obstetric unit) per NICE CG190
• One-to-one midwifery care in established labour
• Mobilisation and upright positions encouraged
• Hydration and light diet in early labour
• Water immersion for pain relief (birthing pool)
• Breathing techniques, massage, TENS

Pharmacological

• Entonox (50% nitrous oxide / 50% oxygen): inhaled, self-administered
• Pethidine 100-150mg IM or diamorphine 5-7.5mg IM (opioid analgesia)
• Epidural analgesia: bupivacaine 0.1% with fentanyl 2 mcg/mL (effective but requires continuous CTG)
• Oxytocin augmentation if delay in first stage: start at 1-2 mU/min, titrate every 30 minutes (requires continuous CTG)
• Active management of third stage: oxytocin 10 IU IM with delivery of anterior shoulder or immediately after delivery

Surgical/Interventional

• Amniotomy (ARM) to augment labour if slow progress
• Episiotomy if clinically indicated (mediolateral in UK practice)
• Instrumental delivery (ventouse or forceps) for prolonged second stage or fetal compromise
• Emergency caesarean section if required

Referral Criteria

• Transfer from midwifery-led unit to obstetric unit if complications arise
• Senior obstetric review if partogram action line crossed
• Neonatal team if meconium, prematurity, or fetal compromise

• Spontaneous vaginal delivery rate in UK: approximately 52-58%
• Instrumental delivery rate: 12-15%
• Emergency caesarean rate: 15-16%
• Perineal tear rates: first degree 35%, second degree 30%, third/fourth degree (OASI) 2.9% overall
• PPH (>500 mL) occurs in approximately 5-10% of vaginal deliveries
• Maternal mortality from direct obstetric causes: approximately 4 per 100,000 maternities in the UK
• Neonatal outcomes excellent for term, uncomplicated vaginal delivery

Stages of Labour Summary

Birthplace Study Key Findings

Key Facts

Induction of labour is the process of artificially stimulating uterine contractions to achieve vaginal delivery before spontaneous onset of labour. It is one of the most commonly performed obstetric interventions.

Epidemiology

• IOL rate in the UK: approximately 33% of all births (rising trend)
• Most common indication: post-dates pregnancy (>41 weeks)
• Success rate for vaginal delivery after IOL: approximately 70-80%

Aetiology (Indications)

• Post-dates pregnancy (≥41+0 weeks) - most common
• Pre-eclampsia / gestational hypertension
• Diabetes (gestational or pre-existing)
• Fetal growth restriction
• PROM at term (>24 hours without spontaneous onset)
• Obstetric cholestasis
• Multiple pregnancy
• Maternal request (after 39 weeks following counselling)
• Intrauterine fetal death

Pathophysiology

• Prostaglandins (PGE2, PGE1) cause cervical ripening through collagenase activation and increase in hyaluronic acid
• Prostaglandins also stimulate myometrial contractions
• Oxytocin stimulates uterine contractions via oxytocin receptors (upregulated at term)
• Amniotomy releases prostaglandins from the membranes and increases local oxytocin release

Pre-induction Assessment

• Confirm indication and gestation
• Assess Bishop score (cervical dilatation, effacement, consistency, position, station)
• Confirm fetal presentation (cephalic)
• Baseline CTG
• Exclude contraindications

During Induction

• Onset of regular uterine contractions
• Progressive cervical dilatation
• Spontaneous or artificial rupture of membranes

Red Flags / Complications

• Uterine hyperstimulation: >5 contractions in 10 minutes with or without fetal heart rate changes
• Pathological CTG
• Cord prolapse (particularly after ARM with high presenting part)
• Uterine rupture (especially with previous CS)
• Failed induction (failure to establish labour after full IOL process)

Bedside

• Modified Bishop score assessment (vaginal examination)
• CTG (baseline and during IOL)
• Blood pressure, temperature, pulse
• Confirm fetal presentation (palpation ± ultrasound)

Bloods

• Group and save
• FBC if clinically indicated
• U&Es, LFTs if pre-eclampsia is the indication

Imaging

• Ultrasound for fetal presentation confirmation, liquor volume, EFW if indicated

Special Tests

• None routinely required beyond Bishop score

Non-pharmacological

• Membrane sweep: offered from 40 weeks in nulliparous and 41 weeks in multiparous (NICE NG207); reduces need for formal IOL
• Mechanical cervical ripening: Foley catheter balloon (30-80mL) or double balloon catheter inserted through cervix
• Amniotomy (ARM): performed when cervix sufficiently dilated (Bishop ≥6)

Pharmacological

• Vaginal prostaglandins (cervical ripening if Bishop <6):
  • Dinoprostone (PGE2): 2mg gel or 10mg controlled-release pessary (Propess), repeat gel at 6 hours if needed
  • Misoprostol (PGE1): 25-50mcg vaginal (lower dose if previous CS)
• Oxytocin infusion (after ARM, for augmentation): start at 1-2 mU/min, increase every 30 minutes to max 32 mU/min
• Tocolysis for hyperstimulation: remove Propess pessary, terbutaline 250mcg SC or salbutamol nebuliser

Surgical/Interventional

• ARM performed with amnihook when cervix favourable
• Instrumental delivery or CS if required during IOL
• Emergency CS for failed IOL, fetal compromise, or uterine rupture

Referral Criteria

• Failed IOL: consultant obstetrician review to discuss options (further attempt, caesarean section)
• Uterine hyperstimulation not responding to simple measures
• Abnormal CTG: senior obstetric and midwifery review

• Success rate for vaginal delivery after IOL: 70-80% overall
• Bishop score >6: >90% success for vaginal delivery
• Bishop score <3: higher CS rate (~30-40%)
• IOL at 41 weeks reduces perinatal mortality without increasing CS rate (NICE NG207)
• Uterine hyperstimulation: 1-5% (higher with prostaglandins)
• Uterine rupture with IOL in previous CS: approximately 0.5% (higher with prostaglandins than mechanical methods)
• Cord prolapse after ARM: <1%

Modified Bishop Score

Key Trials

Key Facts

Instrumental delivery refers to the use of forceps or vacuum extractor to assist vaginal delivery during the second stage of labour. It is a core obstetric skill required when spontaneous delivery is not progressing or when expedited delivery is needed.

Epidemiology

• Instrumental delivery rate in the UK: 12-15% of all births
• Ventouse accounts for approximately 60% and forceps 40% of instrumental deliveries
• Higher rates in nulliparous women, epidural use, and occipitoposterior position
• Declining slightly with increasing caesarean section rates

Aetiology (Indications)

• Prolonged second stage: nulliparous >2 hours active pushing, multiparous >1 hour
• Fetal compromise: pathological CTG in second stage
• Maternal exhaustion
• Maternal medical conditions: avoid Valsalva (cardiac disease, intracranial pathology, hypertensive crisis)
• Aftercoming head of breech (forceps only)

Pathophysiology

• Ventouse creates a chignon (artificial caput) on the fetal scalp; traction assists descent and delivery
• Forceps cradle the fetal head; traction and (if rotational) rotation aid delivery
• Force is applied along the pelvic curve to follow the axis of the birth canal

Assessment Before Instrumental Delivery

• Confirm full dilatation
• Assess fetal position (OA, OP, OT - clinical and/or ultrasound)
• Station: at or below ischial spines
• Adequate contractions
• Adequate analgesia (pudendal block for ventouse, regional/spinal for mid-cavity/rotational)
• Empty bladder (catheterise)
• Informed consent

Classification of Instrumental Delivery

• Outlet: fetal scalp visible, minimal rotation needed
• Low-cavity: station at +2cm or more, ≤45° rotation
• Mid-cavity: station above +2cm but head engaged, may need >45° rotation

Red Flags

• Head not engaged (above ischial spines) - contraindication
• Unknown fetal position
• Prematurity (<34 weeks for ventouse due to risk of subgaleal haemorrhage)
• Suspected fetal bleeding disorder
• Failure to deliver with 3 pulls or 3 cup detachments

Bedside

• Abdominal palpation (fifths palpable - must be 0/5 or 1/5)
• Vaginal examination (position, station, moulding, caput, dilatation)
• CTG assessment
• Ultrasound for fetal position if uncertain
• Catheterise bladder

Bloods

• Group and save (should already be available)
• Paired cord blood gases after delivery (arterial and venous)

Imaging

• Intrapartum ultrasound increasingly used to confirm fetal position before instrumental delivery

Special Tests

• Fetal blood sampling may have been performed if CTG concerns preceded decision for instrumental delivery

Non-pharmacological

• Informed consent (including discussion of risks, alternative of CS)
• Appropriate birth setting (theatre for mid-cavity or rotational, may be room for outlet)
• Neonatal team present or on standby
• Paediatrician present for all mid-cavity and rotational deliveries

Pharmacological

• Analgesia: pudendal block + perineal infiltration (outlet ventouse), spinal/epidural (mid-cavity/rotational forceps)
• Oxytocin: may be started/continued for uterine contractions
• Active management of third stage: oxytocin 10 IU IM

Surgical/Interventional

• Ventouse (vacuum): Kiwi cup, metal cup (Malmström), or silicone cup applied to flexion point
• Forceps: Neville Barnes or Simpson's (non-rotational), Kielland's (rotational), Wrigley's (outlet/at CS)
• Episiotomy: mediolateral episiotomy recommended for forceps delivery
• Sequential instrumentation: ventouse followed by forceps is associated with increased neonatal morbidity - should only be performed by senior obstetrician
• Trial of instrumental in theatre: mid-cavity or uncertain deliveries with immediate access to CS if unsuccessful

Referral Criteria

• Failed instrumental delivery: immediate caesarean section
• Third/fourth degree tear: repaired by experienced operator in theatre
• Neonatal assessment after all instrumental deliveries
• Follow-up at 6-12 weeks for perineal clinic if significant tear

• Overall success rate: ventouse 80-85%, forceps 90-95%
• 3rd/4th degree perineal tear: 8-12% with forceps, 4-6% with ventouse
• Neonatal cephalhaematoma: 6-12% with ventouse
• Neonatal subgaleal haemorrhage: 0.6% with ventouse (potentially life-threatening)
• Neonatal facial nerve palsy: 0.5-1% with forceps (usually temporary)
• Maternal urinary incontinence: increased risk with forceps
• Subsequent delivery: 70-80% achieve spontaneous vaginal delivery

Ventouse vs Forceps Comparison

RCOG Classification of Instrumental Delivery

Key Facts

Caesarean section is the most commonly performed major abdominal surgery worldwide. In the UK, approximately one-third of all deliveries are by CS, divided roughly equally between elective (planned) and emergency procedures.

Epidemiology

• UK CS rate: approximately 30-35% (has risen from 12% in 1990)
• Elective (Category 4): approximately 15%
• Emergency (Categories 1-3): approximately 15-20%
• Variation between hospitals (25-40%)
• England CS rate higher than Scotland/Wales

Aetiology (Indications)

• Elective: previous CS (most common), breech presentation, placenta praevia, maternal request, multiple pregnancy (certain presentations), HIV with high viral load
• Emergency: failure to progress in labour, fetal compromise, cord prolapse, placental abruption, uterine rupture, failed instrumental delivery

Pathophysiology

• Surgical delivery through lower uterine segment transverse incision (most common)
• Classical (vertical) incision: used for very preterm, transverse lie, anterior placenta praevia
• Lower segment incision preferred: less blood loss, less adhesion formation, lower rupture risk in subsequent pregnancy

Pre-operative Assessment

• Confirm indication and urgency category
• Consent (including risks of haemorrhage, infection, thromboembolism, injury to bladder/bowel/ureter, future pregnancy implications)
• Blood group and antibody screen
• FBC
• Assessment of anaesthetic suitability

Urgency Classification (NICE CG132)

• Category 1: Immediate threat to life of woman or fetus (decision to delivery within 30 minutes)
• Category 2: Maternal or fetal compromise not immediately life-threatening (within 75 minutes)
• Category 3: No maternal or fetal compromise but early delivery needed
• Category 4: Delivery timed to suit woman and staff (elective)

Red Flags Post-operatively

• Excessive bleeding (PPH >1000 mL)
• Signs of wound infection (erythema, discharge, dehiscence)
• DVT symptoms (unilateral leg swelling, pain)
• PE symptoms (chest pain, dyspnoea)
• Urinary retention or haematuria (bladder injury)
• Abdominal distension (ileus or internal bleeding)

Bedside

• CTG (if in labour or fetal concern)
• Blood pressure, pulse, temperature
• Urinary catheter

Bloods

• FBC
• Group and save / crossmatch (crossmatch for placenta praevia/accreta)
• Coagulation screen if indicated (pre-eclampsia, abruption)

Imaging

• Ultrasound: fetal presentation, placental localisation (if not confirmed)
• MRI: if placenta accreta suspected

Special Tests

• Anaesthetic assessment (airway evaluation, allergies, fasting status)
• VTE risk assessment (all patients)

Non-pharmacological

• WHO surgical safety checklist
• Skin preparation with chlorhexidine
• Urinary catheterisation
• Informed consent (verbal for Cat 1 if written not feasible)
• Partner/support person present (if safe under GA, they should leave)
• Skin-to-skin contact as soon as possible
• Delayed cord clamping (≥1 minute) unless compromised neonate

Pharmacological

• Anaesthesia: spinal (first-line for elective and most emergency), epidural top-up, or general anaesthesia (Cat 1 if no regional in situ)
• Prophylactic antibiotics: IV cefuroxime 1.5g + metronidazole 500mg at induction of anaesthesia (reduces surgical site infection by 65%)
• Oxytocin: 5 IU slow IV at delivery of baby (reduces PPH)
• Thromboprophylaxis: LMWH (e.g., enoxaparin 40mg SC OD) for minimum 10 days post-CS (RCOG GTG 37a); TED stockings
• Analgesia: regular paracetamol 1g QDS + ibuprofen 400mg TDS + rescue opioids (morphine PCA or oral codeine/dihydrocodeine)

Surgical/Interventional

• Skin incision: Joel-Cohen (straight transverse) or Pfannenstiel (curved)
• Uterine incision: lower segment transverse
• Closure: uterus in two layers, peritoneum not closed (CAESAR/CORONIS trials)
• Placenta accreta: may require planned hysterectomy, uterine artery embolisation

Referral Criteria

• Post-CS wound infection: GP review, antibiotics
• Persistent pain or abnormal bleeding: urgent obstetric review
• Subsequent pregnancy: early booking for VBAC counselling
• Mental health support if traumatic delivery experience

• Maternal mortality from CS: approximately 13 per 100,000 (higher than vaginal delivery at 3 per 100,000)
• Surgical site infection: 8-10% (reduced to 3-4% with prophylactic antibiotics)
• PPH (>1000 mL): 4-8%
• VTE: 1-2% without prophylaxis; 0.1% with LMWH
• Bladder injury: 0.1-0.3%
• Uterine rupture in subsequent pregnancy (VBAC): 0.5% with one previous lower segment CS
• VBAC success rate: 72-75%
• Each additional CS increases surgical complexity and risk of placenta accreta

CS Category Classification

VBAC Counselling

Key Facts

Postpartum haemorrhage is the leading cause of maternal mortality worldwide and remains a significant cause of morbidity in the UK. Early recognition and a systematic stepwise approach to management are crucial.

Epidemiology

• Primary PPH (within 24 hours): complicates 5-10% of deliveries
• Minor PPH (500-1000 mL): ~5%
• Major PPH (>1000 mL): ~1-3%
• Secondary PPH (24 hours - 12 weeks): ~1%
• Leading cause of maternal death globally; approximately 1 per 100,000 maternities in the UK

Aetiology (4 T's)

• Tone (70%): uterine atony - overdistended uterus (macrosomia, polyhydramnios, multiple pregnancy), prolonged labour, oxytocin use, chorioamnionitis, grand multiparity
• Trauma (20%): perineal tears, cervical tears, uterine rupture, episiotomy extension
• Tissue (10%): retained placenta, retained products, placenta accreta
• Thrombin (<1%): coagulopathy (DIC, pre-eclampsia, HELLP, inherited bleeding disorders, anticoagulant therapy)

Pathophysiology

• After placental separation, myometrial contraction compresses spiral arteries (living ligatures)
• Failure of uterine contraction (atony) leaves vessels open, causing rapid haemorrhage
• Blood loss can be rapid (up to 500 mL/min from the placental bed)
• Concealed haemorrhage (haematoma formation) may mask true blood loss

Primary PPH

• Visible vaginal bleeding (may be underestimated by 30-50%)
• Boggy, poorly contracted uterus on palpation (atony)
• Tachycardia, hypotension, pallor (signs of hypovolaemia)
• Continuous trickle of blood despite contracted uterus (suggests trauma or retained tissue)

Secondary PPH

• Abnormal vaginal bleeding >24 hours postpartum
• Offensive lochia (infection)
• Uterine tenderness
• Fever

Red Flags

• Blood loss >1000 mL
• Haemodynamic instability (tachycardia >120, systolic BP <90 mmHg)
• Altered consciousness
• Inability to achieve a contracted uterus
• Ongoing bleeding despite uterotonics
• Signs of DIC (oozing from IV sites, widespread petechiae)

Bedside

• ABCDE assessment
• Weigh swabs and measure blood in suction (quantitative blood loss)
• Bimanual uterine assessment
• Inspect placenta for completeness
• Systematic inspection of genital tract for tears
• Urinary catheter (hourly urine output)

Bloods

• FBC (haemoglobin, platelet count)
• Coagulation screen (PT, APTT, fibrinogen)
• Crossmatch (4-6 units for massive PPH)
• U&Es, LFTs
• ABG/VBG (lactate, base excess)
• Point-of-care testing: ROTEM/TEG if available

Imaging

• Ultrasound: retained products, uterine inversion, broad ligament haematoma
• CT angiography if considering embolisation

Special Tests

• Kleihauer test if RhD-negative
• Blood bank: activate massive transfusion protocol if needed

Non-pharmacological

• Call for help early (obstetric emergency team)
• ABCDE approach with simultaneous resuscitation
• Two large-bore IV cannulae (14G)
• Uterine massage (rubbing up a contraction)
• Empty bladder (catheterise)
• Bimanual uterine compression if severe
• Keep patient warm (prevent hypothermia)

Pharmacological

• First-line: Oxytocin 10 IU slow IV or 40 IU in 500 mL saline infusion
• Second-line: Ergometrine 500mcg IM/IV (avoid in hypertension/pre-eclampsia)
• Third-line: Carboprost (Hemabate) 250mcg IM every 15 min (max 8 doses; avoid in asthma)
• Misoprostol 800mcg sublingual/rectal (if other agents unavailable)
• Tranexamic acid 1g IV (give within 3 hours - WOMAN trial: reduced death from bleeding by 19%)
• Blood products: packed red cells, FFP, platelets, cryoprecipitate (target fibrinogen >2 g/L)
• Massive transfusion protocol: 1:1:1 ratio of RBC:FFP:platelets

Surgical/Interventional

• Intrauterine balloon tamponade (Bakri balloon, Rusch catheter)
• B-Lynch compression suture (uterine compression suture)
• Uterine artery ligation (bilateral)
• Internal iliac artery ligation
• Uterine artery embolisation (interventional radiology if available and patient stable)
• Peripartum hysterectomy (life-saving last resort)
• Manual removal of placenta under regional/GA if retained

Referral Criteria

• All major PPH requires consultant obstetrician attendance
• Interventional radiology for uterine artery embolisation
• Haematology for massive transfusion/DIC
• ITU for haemodynamic instability
• Debrief and psychological support post-event

• Active management of third stage reduces PPH by 60%
• Maternal mortality from PPH in UK: approximately 1 per 100,000 maternities
• Tranexamic acid within 3 hours: reduces death from bleeding by 19% (WOMAN trial)
• Hysterectomy rate for massive PPH: ~1 per 2,000 deliveries
• Sheehan syndrome (postpartum hypopituitarism): rare long-term complication of massive PPH
• Recurrence risk: 8-15% in subsequent pregnancies
• Psychological impact: PTSD, postnatal depression, fear of subsequent pregnancy

4 T's of PPH

WOMAN Trial Summary

Massive Transfusion Targets

Key Facts

Retained placenta is a significant cause of postpartum haemorrhage and occurs when the placenta fails to separate or be delivered within the expected timeframe after birth of the baby.

Epidemiology

• Incidence: approximately 1-3% of vaginal deliveries
• Higher incidence with preterm delivery and in certain populations
• Accounts for significant proportion of PPH requiring intervention

Aetiology

• Placenta adherens: most common; placenta has separated but is retained due to inadequate uterine contraction or a closed cervix
• Trapped placenta: placenta has separated but is trapped behind a closing cervix
• Placenta accreta spectrum: abnormal placental invasion into the myometrium preventing normal separation

Pathophysiology

• Normal third stage: uterine contractions reduce placental bed area, causing shearing and placental separation at the decidua spongiosa layer
• Retained placenta occurs when this process fails due to: inadequate contraction (atony), cervical spasm (trapping separated placenta), or abnormal implantation (accreta)
• Risk of haemorrhage increases with time as the uterus cannot fully contract around the bleeding placental site

Typical Presentation

• Placenta not delivered within expected timeframe (30 min with active management)
• Cord signs of separation may or may not be present (cord lengthening, small gush of blood, uterus becomes firmer and rises)
• Ongoing vaginal bleeding
• Cord may snap during controlled cord traction

Red Flags

• Heavy ongoing vaginal bleeding
• Signs of hypovolaemia (tachycardia, hypotension)
• Signs of uterine inversion (if excessive traction applied)
• Difficulty during manual removal (suggests accreta)
• Signs of infection (if prolonged retention)

Bedside

• Assess vital signs (blood loss estimation)
• Palpate uterus (assess contraction and fundal height)
• Examine any delivered placental tissue for completeness
• IV access (two large-bore cannulae)

Bloods

• FBC
• Group and save / crossmatch
• Coagulation screen

Imaging

• Ultrasound: may help distinguish type of retained placenta and guide management
• Doppler USS: useful if accreta suspected

Special Tests

• None routinely required; histological examination of placenta after removal

Non-pharmacological

• Ensure empty bladder (catheterise)
• Attempt breastfeeding (endogenous oxytocin release)
• Controlled cord traction (do not pull excessively - risk of uterine inversion)
• If haemorrhage: ABCDE approach, resuscitation

Pharmacological

• Oxytocin 20 IU in 20 mL saline via umbilical vein injection (Pipingas technique): may promote separation
• IV oxytocin infusion (40 IU in 500 mL over 4 hours)
• Glyceryl trinitrate (GTN) sublingual 400-800mcg may relax cervical spasm (limited evidence)

Surgical/Interventional

• Manual removal of placenta (MROP): performed in theatre under regional (spinal/epidural top-up) or general anaesthesia
• Technique: hand inserted into uterus, fingers used to separate placenta from uterine wall in the cleavage plane
• Prophylactic antibiotics at time of MROP (e.g., co-amoxiclav 1.2g IV)
• If accreta suspected and placenta cannot be separated: do not force - may require hysterectomy or conservative management (leaving placenta in situ with methotrexate - specialist centres only)
• Active management of third stage after MROP (oxytocin, uterine massage)

Referral Criteria

• Consultant obstetrician involvement for all MROP
• Anaesthetic team for theatre
• Blood bank alert for potential major haemorrhage
• If accreta diagnosed: refer to specialist centre

• MROP successful in majority of cases (>95% for adherens/trapped placenta)
• PPH at time of retained placenta: ~40%
• Recurrence risk in subsequent pregnancies: 8-15%
• Placenta accreta: if unsuspected, can cause massive haemorrhage requiring hysterectomy
• Endometritis risk increased after MROP (5-10%)
• Long-term fertility generally unaffected
• If conservative management of accreta: resolution over weeks-months with risk of infection, haemorrhage, and need for delayed hysterectomy

Types of Retained Placenta

Key Facts

Postnatal depression is a depressive illness occurring in the first year after childbirth. It is common, frequently underdiagnosed, and can have significant effects on the mother, her relationship with her baby, and the child's development.

Epidemiology

• Prevalence: 10-15% of women in the first postnatal year
• Onset typically within first 3 months but can occur up to 12 months postpartum
• Baby blues: affects 50-80% of women, onset day 3-5, resolves within 2 weeks
• Paternal PND: affects approximately 5-10% of fathers
• Recurrence risk: 30-50% in subsequent pregnancies

Aetiology

• Biological: hormonal changes (rapid fall in oestrogen and progesterone), HPA axis dysregulation, thyroid dysfunction, genetic predisposition
• Psychological: previous mental health problems, personality factors, unrealistic expectations of parenthood
• Social: lack of social support, relationship difficulties, domestic violence, financial stress, adverse life events, unplanned pregnancy

Pathophysiology

• Rapid decline in reproductive hormones postpartum affects serotonergic and GABAergic neurotransmission
• HPA axis hyperactivity and elevated cortisol levels
• Inflammatory markers (IL-6, TNF-α) are elevated in PND
• Sleep deprivation and disrupted circadian rhythms contribute
• Neuroimaging shows altered activity in prefrontal cortex, amygdala, and anterior cingulate cortex

Core Symptoms

• Persistent low mood (most of the day, nearly every day for ≥2 weeks)
• Anhedonia (loss of interest or pleasure)
• Fatigue and reduced energy

Associated Symptoms

• Sleep disturbance (beyond normal infant-related sleep disruption)
• Appetite changes (usually decreased)
• Poor concentration and indecisiveness
• Feelings of guilt, worthlessness, or inadequacy as a mother
• Anxiety (often prominent - worry about baby's health, own competence)
• Reduced bonding with baby
• Social withdrawal
• Irritability

Red Flags

• Suicidal ideation or plans
• Thoughts of harming the baby
• Self-neglect or neglect of baby
• Psychotic symptoms (hallucinations, delusions) → consider puerperal psychosis
• Rapidly escalating symptoms
• Previous history of bipolar disorder or psychosis

Bedside

• Edinburgh Postnatal Depression Scale (EPDS): score ≥13 suggests depression; question 10 specifically asks about self-harm
• PHQ-9: alternative screening tool
• GAD-7: assess co-morbid anxiety
• Risk assessment: suicidality, thoughts of harming baby, safeguarding concerns

Bloods

• TFTs: exclude hypothyroidism (postpartum thyroiditis)
• FBC: exclude anaemia (common postpartum)
• Ferritin: iron deficiency can mimic or exacerbate depression

Imaging

• Not routinely indicated

Special Tests

• Formal psychiatric assessment if severe or psychotic features
• Social assessment (housing, finances, support network)

Non-pharmacological

• Guided self-help (computerised CBT, self-help books): first-line for mild PND (NICE CG192)
• CBT: first-line for moderate PND; 8-12 sessions
• Interpersonal therapy (IPT): evidence-based for PND
• Peer support and mother-and-baby groups
• Practical support: help with childcare, sleep strategies
• Exercise (moderate regular exercise has evidence for improving mood)
• Partner and family involvement

Pharmacological

• Mild-moderate: psychological therapy preferred first
• Moderate-severe or failed psychological therapy: SSRI antidepressant
  • Sertraline 50-200mg OD (first-line in breastfeeding - lowest milk transfer)
  • Alternative: fluoxetine 20mg OD, paroxetine 20mg OD (higher milk transfer)
• Continue antidepressant for ≥6 months after remission, then gradual withdrawal
• If previous PND: consider prophylactic antidepressant in third trimester or immediately postpartum
• Severe/psychotic depression: specialist perinatal mental health team; may need antipsychotic, lithium

Surgical/Interventional

• Not applicable

Referral Criteria

• Specialist perinatal mental health team: severe depression, psychotic features, significant risk, history of bipolar
• Mother and Baby Unit (MBU): if inpatient admission needed (keeps mother and baby together)
• Crisis team: suicidal ideation, acute safety concerns
• Safeguarding: if concerns about baby's safety
• Health visitor: ongoing community monitoring and support

• With treatment, majority of women recover fully
• Untreated PND: 50% still depressed at 6 months, 25% at 12 months
• Recurrence risk in subsequent pregnancy: 30-50%
• Impact on child: impaired bonding, delayed cognitive and emotional development, behavioural problems
• Increased risk of chronic depression: 40% of women with PND develop recurrent depression
• Paternal PND associated with poorer child outcomes
• Early identification and treatment significantly improves outcomes for mother and baby

Differentiating Postnatal Mood Disorders

Edinburgh Postnatal Depression Scale

Key Facts

Puerperal (postpartum) psychosis is the most severe form of postnatal mental illness. It is a psychiatric emergency with significant risk to both mother and baby, requiring prompt recognition and specialist treatment.

Epidemiology

• Incidence: 1-2 per 1,000 deliveries
• Onset typically within first 2 weeks postpartum (peak days 3-7)
• Up to 75% of cases in the first 4 weeks
• Suicide is a leading cause of direct maternal death in the UK (MBRRACE-UK)
• Infanticide risk: approximately 4% (uncommon but must be assessed)

Aetiology

• Bipolar affective disorder: strongest risk factor (25-50% recurrence risk per pregnancy)
• Previous puerperal psychosis (recurrence risk 25-57%)
• Family history of puerperal psychosis or bipolar disorder
• Primiparity
• Sleep deprivation
• Caesarean section (possibly through sleep disruption)
• Genetic factors: linkage to chromosome 16 in some families

Pathophysiology

• Exact mechanisms unclear; likely multifactorial
• Rapid postpartum hormonal changes (oestrogen, progesterone withdrawal) trigger episode in genetically vulnerable women
• Hypersensitivity of dopamine receptors in postpartum period
• Sleep deprivation may be a precipitating factor
• Immune system changes postpartum may contribute
• Strong genetic component: first-degree relative with puerperal psychosis increases risk 100-fold

Typical Presentation

• Acute onset within days of delivery (often day 3-7)
• Rapidly fluctuating presentation with lucid intervals
• Confusion and perplexity (distinguishing feature from non-puerperal psychosis)
• Elated or irritable mood (manic features common)
• Delusions (often related to the baby - believing baby is divine, dead, or not theirs)
• Hallucinations (auditory or visual; may include command hallucinations regarding the baby)
• Agitation and bizarre behaviour
• Insomnia (beyond normal newborn sleep disruption)

Red Flags

• Any psychotic symptoms in the postpartum period
• Command hallucinations (particularly regarding the baby)
• Delusional beliefs about the baby
• Suicidal ideation or plans
• Thoughts of harming the baby
• Rapidly escalating symptoms
• Refusal to eat/drink or care for baby
• Previous bipolar or puerperal psychosis

Bedside

• Comprehensive mental state examination
• Risk assessment (suicide, infanticide, self-neglect)
• Physical examination (exclude organic causes)
• Vital signs including temperature
• Urinalysis

Bloods

• FBC, CRP (exclude infection/sepsis)
• U&Es, calcium (metabolic derangement)
• TFTs (thyroid dysfunction common postpartum)
• LFTs
• Blood glucose
• Blood cultures if pyrexial
• Urine drug screen

Imaging

• CT/MRI head if diagnostic uncertainty or focal neurology
• Not routinely required if classic presentation

Special Tests

• Electroencephalogram (EEG) if seizures suspected
• Autoimmune encephalitis antibodies if atypical presentation
• Lumbar puncture if meningitis/encephalitis suspected

Non-pharmacological

• Urgent psychiatric assessment (ideally by specialist perinatal mental health team)
• Admission to Mother and Baby Unit (MBU): preferred setting (keeps mother and baby together with specialist supervision)
• If MBU unavailable: general psychiatric ward with arrangements for supervised baby contact
• One-to-one nursing observation
• Ensure baby safety (supervised contact, risk assessment)
• Involve partner/family in care plan
• Practical support with infant care

Pharmacological

• Antipsychotics (acute psychosis):
  • Olanzapine 5-20mg OD (sedating, caution with breastfeeding)
  • Haloperidol 2-10mg PO/IM (if breastfeeding preferred; lower milk transfer)
  • Quetiapine 25-800mg OD (alternative)
• Mood stabilisers:
  • Lithium (first-line for relapse prevention and acute treatment of manic symptoms; contraindicated in breastfeeding)
  • Valproate (AVOID in women of childbearing potential - teratogenic)
• Benzodiazepines: short-term for agitation and insomnia (e.g., lorazepam 1-2mg PO/IM)
• Electroconvulsive therapy (ECT): effective for severe cases, rapid response, safe in postpartum period

Surgical/Interventional

• ECT: considered for severe, treatment-resistant cases; particularly effective for puerperal psychosis

Referral Criteria

• All cases: urgent referral to specialist perinatal mental health team
• MBU admission (national bed finder service available)
• If no MBU bed: general psychiatric admission with safeguarding plan for baby
• Community perinatal team for follow-up after discharge
• Preconception counselling for future pregnancies
• Genetic counselling if family history suggestive

• Majority recover fully from the acute episode (over weeks to months)
• Average inpatient stay: 6-8 weeks
• ECT provides rapid improvement in many cases
• Recurrence risk: 25-57% in subsequent pregnancies; higher (up to 50%) if underlying bipolar disorder
• 50% of women with puerperal psychosis are later diagnosed with bipolar affective disorder
• Risk of non-puerperal psychiatric episodes: 70-80% over lifetime
• With prophylactic treatment (lithium from third trimester/immediately postpartum): recurrence risk reduced to 10-20%
• Mother-infant bonding usually recovers fully with appropriate support
• Infanticide: rare (~4%) but must be actively risk-assessed

Comparison of Postnatal Mental Health Conditions

Prevention in High-Risk Women

Key Facts

Venous thromboembolism in pregnancy encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE). Pregnancy is a prothrombotic state due to Virchow's triad: hypercoagulability, venous stasis, and endothelial injury. VTE remains the leading direct cause of maternal death in the UK.

Epidemiology

• Incidence: 1-2 per 1,000 pregnancies
• Risk is present throughout pregnancy and the puerperium, with highest risk in the first 6 weeks postpartum
• Accounts for approximately 1.13 deaths per 100,000 maternities in the UK (MBRRACE-UK 2020)
• DVT is more common antepartum; PE is more common postpartum
• Left-sided DVT predominates (85%) due to compression of the left common iliac vein by the right iliac artery

Aetiology

• Hypercoagulability: increased levels of factors VII, VIII, X, fibrinogen, von Willebrand factor; decreased protein S; acquired resistance to activated protein C
• Venous stasis: compression of pelvic veins by the gravid uterus; hormonally mediated venodilation
• Endothelial injury: during delivery, particularly caesarean section
• Additional risk factors: previous VTE, known thrombophilia (Factor V Leiden, prothrombin gene mutation, antithrombin deficiency, antiphospholipid syndrome), obesity (BMI >30), immobility, pre-eclampsia, dehydration, long-haul travel

Pathophysiology

• Pregnancy induces a physiological hypercoagulable state to minimise blood loss at delivery
• Venous stasis worsens as the uterus enlarges, compressing the IVC and iliac veins
• Thrombus formation typically begins in the deep veins of the calf or iliofemoral segment
• Embolisation to the pulmonary vasculature causes PE with ventilation-perfusion mismatch and, in severe cases, right ventricular failure

Deep Vein Thrombosis

• Unilateral leg swelling (>2 cm difference in calf circumference)
• Pain and tenderness, particularly in the calf or thigh
• Erythema and warmth
• Left leg affected in 85% of cases
• Symptoms may overlap with normal pregnancy-related leg swelling

Pulmonary Embolism

• Sudden-onset dyspnoea (most common symptom)
• Pleuritic chest pain
• Tachycardia and tachypnoea
• Haemoptysis
• Collapse or cardiac arrest in massive PE

Red Flags

• Sudden-onset dyspnoea with pleuritic chest pain
• Haemodynamic instability (massive PE)
• Oxygen saturations <94%
• Signs of right heart strain
• Unilateral leg swelling with pain at any stage of pregnancy or within 6 weeks postpartum

Bedside

• Oxygen saturations and ABG if PE suspected
• ECG (sinus tachycardia most common; S1Q3T3 pattern, right axis deviation in PE)
• Chest X-ray (to exclude other causes; often normal in PE)
• Leg circumference measurements (>2 cm difference is significant)

Bloods

• FBC, U&Es, LFTs
• Coagulation screen
• D-dimer is NOT reliable in pregnancy (physiologically elevated); do not use to exclude VTE
• Thrombophilia screen (defer to 6 weeks postpartum; not done acutely)

Imaging

• Compression duplex USS: first-line for suspected DVT; sensitivity >95% for proximal DVT
• If USS negative but high clinical suspicion: repeat in 3-7 days or perform MR venography
• CTPA: preferred investigation for PE in pregnancy (RCOG GTG 37b); higher sensitivity and specificity than V/Q scan
• V/Q scan: alternative if CTPA contraindicated; lower radiation dose to maternal breast tissue

Special Tests

• Echocardiography if massive PE (right ventricular dilatation, McConnell's sign)
• MR venography for iliac vein thrombosis if USS equivocal

Non-pharmacological

• Elevate affected leg and apply graduated compression stockings (after excluding arterial disease)
• Early mobilisation once anticoagulated
• Adequate hydration
• Risk assessment using RCOG VTE risk assessment tool at booking, during admission, and postpartum

Pharmacological

• LMWH is the treatment of choice:
  • Enoxaparin 1mg/kg BD (treatment dose) or 1.5mg/kg OD
  • Dalteparin 200 units/kg OD or 100 units/kg BD
  • Tinzaparin 175 units/kg OD
• Continue treatment dose LMWH throughout pregnancy and for at least 6 weeks postpartum (minimum total duration 3 months)
• Switch to unfractionated heparin around delivery if epidural/spinal planned (shorter half-life)
• Warfarin is teratogenic in first trimester (avoid); may be used postpartum (safe in breastfeeding)
• DOACs are contraindicated in pregnancy and breastfeeding
• Thrombolysis (alteplase 50mg IV) for massive PE with haemodynamic compromise

Surgical/Interventional

• Surgical embolectomy or catheter-directed thrombolysis for life-threatening PE unresponsive to medical therapy
• IVC filter in rare cases where anticoagulation is contraindicated and recurrent PE

Referral Criteria

• Immediate referral to obstetric medicine/haematology for confirmed VTE
• Anaesthetic review for delivery planning (timing of LMWH cessation)
• Thrombophilia screening at 6 weeks postpartum
• Postnatal review to determine duration of anticoagulation

• Maternal mortality from PE: approximately 1-2% with treatment
• Case fatality rate for untreated PE: 30%
• Recurrence risk in subsequent pregnancies: 5-12% (higher with thrombophilia)
• Post-thrombotic syndrome develops in 20-50% of DVT cases
• Long-term anticoagulation may be required if recurrent VTE or high-risk thrombophilia
• With appropriate thromboprophylaxis, risk of recurrence is significantly reduced

RCOG VTE Risk Assessment

LMWH Dosing for Thromboprophylaxis (Weight-Based)

Peripartum LMWH Management

Key Facts

Ectopic pregnancy is the implantation of a fertilised ovum outside the endometrial cavity. It is a common and potentially life-threatening condition requiring prompt diagnosis and management. Early recognition is essential to prevent tubal rupture and haemodynamic compromise.

Epidemiology

• Incidence: approximately 11 per 1,000 pregnancies in the UK
• Accounts for 0.5% of maternal deaths in the UK
• Peak incidence at age 25-34 years
• Incidence rising due to increased prevalence of risk factors and earlier detection

Aetiology

• Tubal factors: previous PID/salpingitis (especially Chlamydia trachomatis), previous tubal surgery, previous ectopic pregnancy (10-15% recurrence), tubal endometriosis
• Contraceptive factors: progesterone-only pill, IUCD/IUS in situ (does not increase absolute risk but proportion of ectopics increases), previous sterilisation failure
• Assisted reproduction: IVF/ICSI (2-5% ectopic rate)
• Other: smoking (dose-dependent, 2× risk), age >35 years, history of infertility

Pathophysiology

• 97% are tubal: ampullary (70%), isthmic (12%), fimbrial (11%), interstitial/cornual (2-4%)
• Non-tubal sites: ovarian (3%), cervical (<1%), caesarean scar, abdominal/peritoneal (rare)
• Damaged tubal epithelium (from PID, surgery) impairs ovum transport
• Growing ectopic erodes into tubal wall and blood vessels
• Tubal rupture causes intraperitoneal haemorrhage and haemodynamic compromise

Typical Presentation

• Amenorrhoea (6-8 weeks, though may have irregular bleeding mistaken for a period)
• Unilateral lower abdominal/pelvic pain
• Vaginal bleeding (usually scanty, dark brown, 'prune juice')
• Pain may be intermittent or constant

Ruptured Ectopic

• Sudden severe abdominal pain
• Shoulder tip pain (diaphragmatic irritation from haemoperitoneum)
• Haemodynamic compromise: tachycardia, hypotension, syncope
• Peritonism: guarding, rebound tenderness
• Cervical excitation on bimanual examination

Red Flags

• Haemodynamic instability (tachycardia, hypotension)
• Shoulder tip pain
• Syncope or collapse
• Peritonism
• Positive pregnancy test with acute abdomen

Bedside

• Urine pregnancy test (highly sensitive, positive in >99%)
• Observations: HR, BP, temperature
• Urinalysis

Bloods

• Serum βhCG: essential for management decisions; level >1,500 IU/L (discriminatory zone) without intrauterine pregnancy on TVS is highly suspicious
• Serial βhCG at 48 hours: in normal IUP, rises by ≥63%; in ectopic, often rises <63% or plateaus/falls
• FBC (haemoglobin for haemorrhage assessment)
• Group and save / crossmatch if haemodynamically unstable
• Serum progesterone: <20 nmol/L suggests non-viable pregnancy (limited utility)

Imaging

• Transvaginal ultrasound (TVS): first-line investigation (NICE NG126)
  • Intrauterine pregnancy visible from βhCG ~1,000-1,500 IU/L
  • Ectopic findings: adnexal mass, 'blob sign', 'bagel sign', tubal ring, free fluid in POD
  • Empty uterus with positive pregnancy test = pregnancy of unknown location (PUL)

Special Tests

• Diagnostic laparoscopy: definitive if diagnosis uncertain and patient symptomatic

Non-pharmacological

• Expectant management: suitable if βhCG <1,500 IU/L and declining, asymptomatic, able to return for follow-up
• Patient information: ectopic pregnancy warning symptoms, when to attend A&E
• Psychological support: early pregnancy loss counselling

Pharmacological

• Methotrexate 50mg/m² IM single dose:
  • Criteria: confirmed ectopic, βhCG <5,000 IU/L (some centres <3,000), no significant pain, adnexal mass <35mm, no fetal cardiac activity, no intrauterine pregnancy
  • Monitor βhCG on days 4 and 7: need ≥15% drop between days 4-7
  • If insufficient decline, consider second dose or surgery
  • Advise reliable contraception for 3 months after methotrexate (teratogenic)
  • Anti-D immunoglobulin for RhD-negative women if surgical management

Surgical/Interventional

• Laparoscopic salpingectomy: first-line surgical treatment (preferred if contralateral tube is healthy)
• Laparoscopic salpingotomy: considered if contralateral tube is damaged/absent (fertility-sparing); requires serial βhCG follow-up for persistent trophoblast
• Emergency laparotomy: for ruptured ectopic with haemodynamic instability

Referral Criteria

• All suspected ectopic pregnancies require urgent assessment in an early pregnancy assessment unit (EPAU)
• Emergency surgical referral if haemodynamically unstable
• Follow-up with serial βhCG until <5 IU/L (expectant or medical management)

• Maternal mortality: 0.2 per 1,000 ectopic pregnancies in the UK (significantly improved with early detection)
• Success rate of methotrexate (single dose): 65-95% (higher with lower initial βhCG)
• Subsequent intrauterine pregnancy rate: 60-70% after salpingectomy, 70-80% after salpingotomy
• Recurrence risk: 10-15% after one ectopic; 25% after two
• Persistent trophoblast after salpingotomy: 5-20% (requires serial βhCG monitoring)

Management Pathway Summary

βhCG Interpretation in Early Pregnancy

Key Facts

Miscarriage is defined as the spontaneous loss of a pregnancy before 24 weeks of gestation. It is the most common complication of early pregnancy. Early pregnancy assessment units (EPAUs) play a central role in diagnosis and management.

Epidemiology

• Affects approximately 25% of all recognised pregnancies
• 80% occur before 12 weeks gestation
• Incidence increases significantly with maternal age
• Chemical pregnancies (very early loss) are even more common but often unrecognised

Aetiology

• Chromosomal abnormalities: 50-60% of sporadic first-trimester miscarriages (trisomy most common, followed by monosomy X and triploidy)
• Maternal factors: advanced age, uterine anomalies (septate uterus), fibroids (submucosal), cervical incompetence
• Endocrine: poorly controlled diabetes, thyroid disease, PCOS
• Thrombophilia: antiphospholipid syndrome (most important treatable cause)
• Infection: bacterial vaginosis, TORCH infections
• Lifestyle: smoking, alcohol, cocaine, high caffeine intake (>300mg/day)

Pathophysiology

• Chromosomal abnormalities lead to abnormal embryo development and spontaneous expulsion
• Antiphospholipid syndrome causes placental thrombosis and infarction
• Cervical incompetence results in painless cervical dilatation typically in the second trimester
• Uterine anomalies impair implantation and placental development

Threatened Miscarriage

• Vaginal bleeding (usually light) with closed cervical os
• May have mild cramping
• Viable pregnancy on USS in 50% of cases

Inevitable Miscarriage

• Heavy vaginal bleeding with open cervical os
• Significant crampy lower abdominal pain
• Products of conception may be visible at the os

Incomplete Miscarriage

• Passage of some products of conception
• Continued bleeding and pain
• Open cervical os with retained tissue on USS

Missed Miscarriage

• Embryo has died but not yet expelled
• May have brown discharge or no symptoms
• Often diagnosed incidentally on USS
• CRL ≥7mm with no cardiac activity on TVS (NICE NG126)

Red Flags

• Heavy bleeding with haemodynamic compromise
• Signs of sepsis (septic miscarriage): fever, offensive discharge, tachycardia
• Severe abdominal pain (consider ectopic pregnancy)
• Products of conception at the cervical os (can cause vasovagal collapse - remove with sponge forceps)

Bedside

• Urine pregnancy test
• Observations: HR, BP, temperature
• Speculum examination: assess cervical os, exclude products at os

Bloods

• Serum βhCG: if diagnosis uncertain or pregnancy of unknown location
• FBC: assess for anaemia from blood loss
• Group and save: if significant bleeding
• Rhesus status

Imaging

• Transvaginal ultrasound: gold standard for diagnosis (NICE NG126)
  • Missed miscarriage: CRL ≥7mm with no cardiac activity
  • Empty sac: mean gestational sac diameter ≥25mm with no embryo (anembryonic pregnancy)
  • If findings are uncertain: repeat TVS in minimum 7 days

Special Tests

• Histology of products of conception (confirm pregnancy tissue, exclude molar pregnancy)
• Karyotyping of products if recurrent miscarriage

Non-pharmacological

• Expectant management: first-line for incomplete miscarriage; successful in 50% within 2 weeks
• Provide written information and 24-hour contact details
• Offer psychological support and follow-up
• If products at the cervical os: remove with sponge forceps (can cause vasovagal reaction)

Pharmacological

• Misoprostol 800mcg PV (or 600mcg PO) as a single dose: recommended if expectant management fails or patient preference
• Can repeat misoprostol dose after 48 hours if incomplete expulsion
• Analgesia: NSAIDs (ibuprofen 400mg TDS), paracetamol, codeine for pain
• Anti-D immunoglobulin: for RhD-negative women if surgical management at any gestation, or medical/expectant management if ≥12 weeks
• Antibiotics: if septic miscarriage (IV amoxicillin, metronidazole, and gentamicin)

Surgical/Interventional

• Manual vacuum aspiration (MVA): can be performed under local anaesthesia in outpatient setting
• Surgical management under general anaesthesia (ERPC): evacuation of retained products of conception
• Indications: patient choice, heavy persistent bleeding, signs of infection, failed medical management

Referral Criteria

• All women with bleeding in early pregnancy should be referred to EPAU (NICE NG126)
• Emergency referral if haemodynamically unstable or septic
• Refer for recurrent miscarriage investigation after 3 consecutive losses (or 2 if age >35)

• After a single miscarriage, chance of successful next pregnancy: 85%
• After two miscarriages: 75%
• After three miscarriages: 65%
• Risk of miscarriage by maternal age: 10% at age 20-24, 20% at age 35-39, 50% at age >45
• Septic miscarriage mortality: <1% with prompt treatment
• Psychological impact: significant; associated with anxiety and depression in subsequent pregnancies

Classification of Miscarriage

TVS Diagnostic Criteria (NICE NG126)

Key Facts

Recurrent miscarriage is the loss of three or more consecutive pregnancies. It requires a systematic approach to investigation to identify treatable causes, although in over 50% of cases no cause is found.

Epidemiology

• Affects approximately 1% of couples
• Risk of further miscarriage after 3 losses: 40% (compared to 20% background risk)
• Age-related: risk increases significantly with maternal age >35

Aetiology

• Antiphospholipid syndrome (APS): 15% of cases; most important treatable cause
• Chromosomal abnormalities: parental balanced translocation in 2-5% of couples; increased embryonic aneuploidy
• Uterine anomalies: septate uterus (most common treatable uterine cause), submucosal fibroids, Asherman syndrome
• Endocrine: poorly controlled diabetes, thyroid dysfunction, PCOS (controversial)
• Thrombophilia: inherited (Factor V Leiden, prothrombin gene mutation) - weaker association than APS
• Unexplained: >50% of cases; likely multifactorial including embryonic aneuploidy

Pathophysiology

• APS: autoantibodies activate complement, cause placental thrombosis and inflammation, impairing trophoblast invasion
• Balanced translocations: phenotypically normal parents produce unbalanced gametes leading to chromosomally abnormal embryos
• Uterine septum: poor vascularisation impairs implantation
• Cervical incompetence: painless cervical dilatation typically in second trimester

Typical History

• Three or more consecutive pregnancy losses before 24 weeks
• Losses may be first trimester (most common) or second trimester
• Pattern of loss can guide investigation (e.g. second-trimester losses suggest cervical incompetence or APS)

Associated Features

• History of thrombosis (DVT, PE, stroke) suggests APS
• Features of autoimmune disease (rash, joint pain)
• Abnormal menstrual pattern
• Previous uterine surgery (ERPC, curettage)

Red Flags

• Painless cervical dilatation in second trimester (cervical incompetence)
• History of thrombotic events (APS)
• Abnormal bleeding pattern suggesting uterine pathology
• Consanguinity (increased risk of chromosomal abnormalities)

Bedside

• BMI assessment
• Blood pressure
• Thyroid examination

Bloods

• Antiphospholipid antibodies (must be positive on 2 occasions at least 12 weeks apart):
  • Lupus anticoagulant
  • Anticardiolipin antibodies (IgG and IgM)
  • Anti-β2 glycoprotein I antibodies (IgG and IgM)
• Parental karyotyping (both partners)
• Thyroid function tests
• FBC, coagulation screen
• Inherited thrombophilia screen (controversial - RCOG suggests limited role)

Imaging

• Pelvic ultrasound: assess uterine anatomy (3D USS superior for uterine anomalies)
• MRI pelvis: gold standard for uterine anomaly classification
• Cervical length assessment: serial TVS if cervical incompetence suspected

Special Tests

• Hysteroscopy: direct visualisation and treatment of intrauterine pathology (septum, adhesions, polyps, fibroids)
• Karyotyping of products of conception (if available from the miscarriage)

Non-pharmacological

• Supportive care: tender loving care in a dedicated early pregnancy clinic improves outcomes (70-75% live birth rate in unexplained recurrent miscarriage)
• Lifestyle modification: stop smoking, reduce alcohol, limit caffeine to <200mg/day, optimise BMI
• Psychological support and counselling

Pharmacological

• Antiphospholipid syndrome: aspirin 75mg OD from positive pregnancy test PLUS LMWH (e.g. enoxaparin 40mg OD) from positive pregnancy test until 6 weeks postpartum; improves live birth rate to ~70%
• Progesterone: micronised progesterone 400mg PV BD from positive pregnancy test to 12 weeks (PRISM trial showed benefit in subgroup with ≥3 prior miscarriages)
• Thyroid replacement: optimise TSH to <2.5 mU/L in first trimester
• Pre-conception folic acid: 400mcg OD (5mg if previous NTD)

Surgical/Interventional

• Hysteroscopic septum resection: for uterine septum (improves outcomes though RCT evidence limited)
• Cervical cerclage: McDonald or Shirodkar suture at 12-14 weeks for cervical incompetence; rescue cerclage if cervical dilatation <4cm
• Myomectomy: for submucosal fibroids distorting the cavity

Referral Criteria

• Refer to specialist recurrent miscarriage clinic after 3 consecutive losses (some clinicians investigate after 2 if age >35)
• Haematology referral for APS management
• Genetics referral if parental translocation identified
• Fertility specialist if concurrent subfertility

• With no identifiable cause and supportive care: 75% live birth rate in next pregnancy
• With APS treated with aspirin and LMWH: 70% live birth rate (vs 40% untreated)
• Parental balanced translocation: 60% chance of healthy pregnancy (genetic counselling essential)
• Cervical cerclage: reduces preterm birth by 25% in those with proven cervical incompetence
• Risk of miscarriage increases with number of prior losses and maternal age

Antiphospholipid Syndrome Diagnostic Criteria (Revised Sapporo/Sydney)

PRISM Trial Summary

Key Facts

Molar pregnancy is the most common form of gestational trophoblastic disease (GTD), characterised by abnormal proliferation of trophoblastic tissue. Prompt diagnosis, evacuation, and βhCG surveillance are essential to detect and treat malignant transformation.

Epidemiology

• UK incidence: approximately 1 in 714 live births
• Complete moles more common than partial moles
• Risk factors: extremes of reproductive age (<16, >45), previous molar pregnancy (1-2% recurrence), Asian ethnicity
• GTN develops in 15-20% of complete moles and 0.5-5% of partial moles

Aetiology

• Complete mole: fertilisation of an empty ovum by a single sperm that duplicates (90% 46XX) or two sperm (10% 46XY); entirely paternal DNA
• Partial mole: fertilisation of a normal ovum by two sperm, resulting in triploid (69 chromosomes); both maternal and paternal DNA present

Pathophysiology

• Abnormal fertilisation leads to excessive trophoblastic proliferation
• Complete mole: diffuse villous oedema with trophoblastic hyperplasia, no embryonic tissue
• Partial mole: focal villous oedema, some normal villi, may contain fetal tissue
• Trophoblastic tissue invades the myometrium and may metastasise (lungs most common)
• βhCG is produced in excess and serves as a tumour marker

Typical Presentation

• Vaginal bleeding in the first trimester (most common symptom, 84%)
• Uterus large for dates (in complete mole)
• Passage of grape-like vesicles (pathognomonic but rare now due to earlier detection)
• Markedly elevated βhCG (often >100,000 IU/L in complete mole)

Associated Features

• Hyperemesis gravidarum (due to very high βhCG)
• Early-onset pre-eclampsia (before 20 weeks - suspect molar pregnancy)
• Hyperthyroidism (βhCG structurally similar to TSH, cross-reacts with TSH receptor)
• Theca lutein cysts (bilateral ovarian enlargement from high βhCG)

Red Flags

• Pre-eclampsia before 20 weeks gestation
• Uterus significantly larger than expected for dates
• Hyperthyroidism symptoms in early pregnancy
• Respiratory symptoms (pulmonary metastases)

Bedside

• Urine pregnancy test (strongly positive)
• Blood pressure (pre-eclampsia before 20 weeks)
• Thyroid examination

Bloods

• Serum βhCG: markedly elevated (often >100,000 IU/L in complete mole)
• TFTs (hyperthyroidism screening)
• FBC (anaemia)
• Group and save
• Coagulation screen
• U&Es, LFTs

Imaging

• Transvaginal ultrasound: snowstorm appearance (complete mole); mixed echogenic mass with cystic spaces (partial mole); may see theca lutein cysts
• CXR: baseline for comparison if GTN develops (pulmonary metastases)

Special Tests

• Histological examination of all products of conception: essential to confirm diagnosis and classify mole type
• Immunohistochemistry: p57 (absent in complete mole, present in partial mole)
• Genotyping/flow cytometry to confirm ploidy

Non-pharmacological

• Register with UK GTD centre (Charing Cross Hospital London or Weston Park Hospital Sheffield)
• Provide written information and support from GTD patient support organisations
• Reliable contraception until βhCG follow-up complete (barrier methods or hormonal; avoid IUCD until βhCG normal)

Pharmacological

• Anti-D immunoglobulin for RhD-negative women
• If hyperthyroid: beta-blockers (propranolol 40mg TDS) for symptom control
• Do not use oxytocic agents before evacuation (risk of trophoblastic embolism)

Surgical/Interventional

• Suction evacuation under ultrasound guidance: treatment of choice for both complete and partial moles
• Avoid medical evacuation (misoprostol) as it may increase risk of GTN and incomplete evacuation
• Second evacuation may be needed if retained products

Referral Criteria

• All confirmed molar pregnancies must be registered with a UK GTD centre
• βhCG follow-up: weekly until normal, then monthly for 6 months from evacuation (complete mole) or from normalisation (if βhCG normalises within 56 days of evacuation for partial mole)
• If βhCG plateaus or rises: refer urgently for GTN assessment and staging

• Complete mole: 80-85% resolve after evacuation; 15-20% develop GTN
• Partial mole: 95-99.5% resolve after evacuation; 0.5-5% develop GTN
• GTN is highly curable with chemotherapy (cure rate >98%)
• Recurrence risk of molar pregnancy: 1-2% after one mole; 15-20% after two moles
• Future fertility: normal pregnancy outcomes expected after complete βhCG follow-up
• Advised to wait until βhCG surveillance is complete before conceiving again

Complete vs Partial Mole Comparison

βhCG Follow-up Protocol (UK GTD Centres)

Key Facts

Rhesus disease (haemolytic disease of the fetus and newborn, HDFN) results from maternal alloimmunisation against the RhD antigen on fetal red blood cells. Prevention with anti-D immunoglobulin prophylaxis has dramatically reduced the incidence.

Epidemiology

• RhD-negative women: approximately 15% of Caucasians in the UK, lower in other ethnic groups
• Prior to routine prophylaxis, HDFN affected 1% of pregnancies
• With current prophylaxis, clinically significant HDFN is rare (<0.4 per 1,000 births)
• Other antibodies (anti-c, anti-Kell) can also cause HDFN but are less common

Aetiology

• Fetomaternal haemorrhage (FMH): transfer of fetal RhD-positive red cells into maternal circulation
• Sensitising events: delivery, miscarriage, TOP, ectopic, APH, amniocentesis, CVS, ECV, abdominal trauma
• Primary exposure produces IgM (does not cross placenta); subsequent exposure produces IgG (crosses placenta)

Pathophysiology

• Maternal anti-D IgG antibodies cross the placenta and bind to RhD-positive fetal red cells
• Opsonised fetal red cells are destroyed in the fetal reticuloendothelial system (extravascular haemolysis)
• Results in fetal anaemia, compensatory extramedullary haematopoiesis (hepatosplenomegaly), and eventually hydrops fetalis
• Hydrops fetalis: generalised oedema, ascites, pleural effusions, pericardial effusions due to cardiac failure
• After birth: neonatal jaundice from unconjugated hyperbilirubinaemia (risk of kernicterus)

Maternal Presentation

• Usually asymptomatic
• Detected by routine antibody screening at booking and 28 weeks
• History of sensitising events

Fetal Presentation

• Fetal anaemia detected by MCA Doppler (non-invasive)
• Fetal hydrops on ultrasound: subcutaneous oedema, ascites, pleural/pericardial effusions, polyhydramnios, placentomegaly
• Reduced fetal movements
• Intrauterine fetal death in severe untreated cases

Neonatal Presentation

• Jaundice within 24 hours of birth (pathological)
• Anaemia (pallor)
• Hepatosplenomegaly
• Hydrops fetalis (severe)

Red Flags

• Anti-D titre rising rapidly (>4 IU/mL or rising by ≥2 dilutions)
• MCA PSV >1.5 MoM
• Features of hydrops fetalis on USS
• Reduced fetal movements

Bedside

• Blood group and antibody screen at booking and 28 weeks
• Kleihauer test after sensitising events (>20 weeks)

Bloods

• Maternal blood group and antibody screen: identify anti-D or other clinically significant antibodies
• Quantify anti-D titre: monitored 4-weekly; referral to fetal medicine if >4 IU/mL
• Cell-free fetal DNA (cffDNA): from 16 weeks, determines fetal RhD status non-invasively from maternal blood
• Kleihauer test: quantifies FMH to guide additional anti-D doses (1 fetal cell per 50 LPF = ~4 mL FMH)

Imaging

• MCA Doppler: peak systolic velocity (PSV) >1.5 MoM indicates moderate-severe fetal anaemia
• Serial USS: fetal growth, liquor volume, signs of hydrops (ascites, oedema, effusions, placentomegaly)

Special Tests

• Fetal blood sampling (cordocentesis): direct measurement of fetal haemoglobin if MCA Doppler abnormal
• Amniocentesis (historical; largely replaced by MCA Doppler and cffDNA)
• Neonatal: DAT (Coombs test), bilirubin, FBC, reticulocyte count, blood film

Non-pharmacological

• Education of RhD-negative women about the importance of anti-D prophylaxis
• Inform about sensitising events and when to seek anti-D
• Early booking and regular antenatal care

Pharmacological

• Routine antenatal anti-D prophylaxis (RAADP): single dose of 1,500 IU IM at 28 weeks (NICE NG156) or two doses of 500 IU at 28 and 34 weeks
• Anti-D for sensitising events: minimum 250 IU before 20 weeks; minimum 500 IU after 20 weeks; within 72 hours
• Postnatal anti-D: 500 IU IM within 72 hours of delivery if baby is RhD-positive; Kleihauer to guide additional doses
• Intrauterine transfusion (IUT): O-negative, irradiated, CMV-negative packed red cells via cordocentesis for severe fetal anaemia before 34 weeks

Surgical/Interventional

• Intrauterine transfusion: performed by fetal medicine specialist under USS guidance
• Early delivery: planned from 34-37 weeks depending on severity and response to IUT
• Neonatal exchange transfusion or phototherapy for hyperbilirubinaemia

Referral Criteria

• Anti-D titre >4 IU/mL: refer to fetal medicine for MCA Doppler monitoring
• Rising antibody levels: 2-4 weekly monitoring in fetal medicine unit
• cffDNA positive for RhD: continue prophylaxis and monitoring
• cffDNA negative for RhD: no further anti-D required (confirmed RhD-negative fetus)

• With routine prophylaxis, incidence of RhD alloimmunisation has fallen from 13% to <1%
• Mild HDFN: excellent prognosis with phototherapy
• Moderate-severe HDFN: good outcomes with intrauterine transfusion (survival >90% in experienced centres)
• Hydrops fetalis without treatment: high mortality (>50%)
• With IUT: survival rates 85-95% in non-hydropic fetuses
• Long-term neurodevelopmental outcomes generally good with appropriate management

Anti-D Dosing Guide

MCA Doppler Interpretation

Key Facts

Group B Streptococcus (GBS, Streptococcus agalactiae) is a Gram-positive coccus that commonly colonises the gastrointestinal and genital tracts. It is the most frequent cause of early-onset neonatal sepsis, meningitis, and pneumonia in the UK.

Epidemiology

• Vaginal/rectal colonisation in 20-30% of pregnant women (transient, intermittent, or chronic)
• Early-onset GBS disease (EOGBS): 0.5 per 1,000 live births in the UK
• Late-onset GBS disease (7-90 days): 0.3 per 1,000 live births
• Vertical transmission rate: 50% of babies born to colonised mothers become colonised; 1-2% of these develop invasive disease

Aetiology

• Ascending infection from the maternal genital tract during labour
• Risk increases with prolonged rupture of membranes, preterm delivery, intrapartum fever
• Previous GBS disease in a sibling is the strongest risk factor