11: Maternal Death Flashcards
Direct causes of maternal death to be considered at autopsy
○ VTE and PE
○ Pre-eclampsia, eclampsia
§ HELLP syndrome in PET (haemolysis, elevated liver enzymes, low platelets)
○ Peripartum haemorrhage
§ a. Uterine atony
§ b. Abruption of the placenta
§ c. Placenta praevia
§ d. Abnormally adherent placenta
§ i. Placenta accreta, increta, percreta
§ e. Retained placenta
§ f. Tear or rupture of genital tract
□ i. Spontaneous
□ ii. Iatrogenic
○ Life support for peripartum haemorrhage
§ a. TRALI (transfusion-associated lung injury)
§ b. Fluid overload
○ Peripartum dilated cardiomyopathy (defined as cardiac failure from last month of pregnancy up to 5 months post-partum; other causes excluded)
○ Amniotic fluid embolism
○ Early pregnancy deaths
§ a. Ectopic pregnancy and haemorrhage
§ b. Spontaneous miscarriage
§ c. Legal termination
○ Genital tract sepsis – puerperal sepsis
○ Anaesthetic (general and regional anaesthesia)
○ Air embolism
○ Ogilvie’s syndrome (pseudo-obstruction of the large bowel)
○ Choriocarcinoma and hydatidiform mole
○ Ovarian hyperstimulation syndrome (OHSS)
○ Acute fatty liver of pregnancy
Indirect causes of maternal death to be considered at autopsy
○ Cardiac
§ a. Congenital heart lesion with pulmonary hypertension
§ b. Inheritable cardiomyopathy, e.g. hypertrophic cardiomyopathy (HOCM), arrhythmogenic right ventricular cardiomyopathy (ARVCM)
§ c. Acquired cardiac muscle disease, e.g. ischaemic heart disease, endocardial fibroelastosis
§ d. Obesity and sudden cardiac death
§ e. Valvular disease, e.g. in IV drug users, rheumatic mitral stenosis
○ Systemic hypertension
○ Idiopathic arterial (primary) pulmonary hypertension
○ Pre-existing thrombophilia states, including antiphospholipid syndrome
○ Thrombotic thrombocytopenic purpura (TTP)
○ Stroke
§ a. Subarachnoid haemorrhage
§ b. Cerebral infarction
§ c. Cerebral venous sinus thrombosis
○ Other cardiovascular diseases
§ a. Dissection of aorta
§ b. Dissection of coronary artery
§ c. Dissection of splenic artery
○ Psychiatric, including suicide related to pregnancy and delivery
○ Epilepsy [sudden unexplained death in epilepsy (SUDEP)]
○ Malignant disease worsened by pregnancy (breast, cervix)
○ Community-acquired sepsis
○ Acute anaphylaxis from drug treatment, e.g. antibiotics
○ Other diseases:
§ a. HIV/AIDS and tuberculosis
§ b. Sickle cell disease (HbSS and HbSC)
§ c. Connective tissue disease systemic lupus erythematosus (SLE)
§ d. Diabetes mellitus – gestational and pre-existing diabetes; this includes the hypoglycaemic ‘dead in bed’ syndrome
§ e. Influenza (e.g. epidemic type A H1N1)
§ f. Cirrhosis
§ g. Any other clinico-pathological condition that the pregnant state makes worse; these include inherited and acquired conditions, and the patient may have been specifically warned of the hazards of becoming pregnant.
Coincidental causes of maternal death to consider at autopsy
○ Death by own hands (suicide – some cases are unrelated to pregnancy, reflecting underlying mental health issues; note that only Coroners/Procurator Fiscals can make the verdict of ‘suicide’)
○ Other malignant disease
○ Stroke (early in pregnancy)
○ Road accident
○ Homicide
○ Toxic/illicit drug overdose
○ Any other significant clinico-pathological condition
What is an ectopic pregnancy and where can they arise?
- Pregnancy that implants outside of the endometrium of the uterus ○ Fallopian tubes § Ampulla = 80% § Isthmus = 12% § Infundibulum § Fimbriae = 5% ○ Ovary ○ Cornu of uterus ○ Abdominal cavity ○ Cervix
What are the risk factors for ectopic pregnancy?
- Previous ectopic pregnancy
- Fertility treatments
- Tubal ligation
- Bicornate uterus
- Altered tubal motility
○ Smoking
○ Hormonal contraception - Chronic salpingitis
○ Pelvic inflammatory disease - Peritubal scarring
○ Appendicitis
○ Endometriosis
○ Abdominal surgery - Intrauterine device
Morphological features of ectopic pregnancy
- Macroscopic ○ Non-ruptured § Enlarged fallopian tube § Foetus in gestational sac § Tubal lumen with mural + luminal haemorrhage ○ Ruptured § Blood clot / haemorrhage - Microscopic ○ Ruptured uterine tube ○ Conceptus expanding tubal wall ○ Copmressed tubal lumen ○ Chorionic villus (foetal tissue) § Cytotrophoblast § Syncytiotrophoblast ○ Fallopian tube lining - ciliated columnar epithelium
Clinical features of ectopic pregnancy
- Expanding mass ○ Pain § Abdomen § Pelvis § Back § Shoulder ○ Vaginal bleeding § Dark brown § 6-8 weeks after MP ○ Tenderness or mass § Cervix § Adnexa - Pregnancy ○ Nausea ○ Vomiting ○ Fatigue ○ Breast tenderness - Rupture ○ Acute abdomen § Distension § Tenderness § Peritonitis ○ Hypovolaemic shock § High heart rate § Decreased BP § Feeling cold § Collapse
Complications of ectopic pregnancy
- Tubal rupture ○ Usually 6 week post-implantation ○ Occurs in 50% of untreated cases - Death - Psychological effects ○ Grief, anxiety, depression ○ Last 6-12 months - Recurrence ○ 18.5% - Methotrexate therapy ○ Adverse drug reactions - Damage to surrounding structures ○ Result of surgical intervention or expanding mass - Persistent trophoblast ○ Commonly seen after salpingostomy ○ Warrant further therapy
What other differential diagnoses should be considered when intra-abdominal haemorrhage is encountered in a maternal death?
- Directly associated with pregnancy ○ Ruptured ectopic pregnancy ○ Ruptured uterus ○ Placenta praevia ○ Placental abruption ○ HELLP syndrome - Indirectly or not associated with pregnancy ○ Endometriosis ○ Ruptured cyst ○ Broad ligament haematoma ○ Vascular aneurysm ○ Splenic rupture
Define pre-eclampsia
- Pre-eclampsia ○ Affects up to 10% of pregnancy ○ Characterised by § Maternal hypertension § Proteinuria § Peripheral oedema § Coagulation abnormalities
Define eclampsia
○ Pre-eclampsia with hyperreflexia and convulsions
○ Potentially life-threatening
Define HELLP syndrome
○ Haemolysis
○ Elevated liver enzymes
○ Low platelets
○ Hypertension also very common
Features required for pre-eclampsia
○ Maternal hypertension, usually with proteinuria, after 20/40
○ >140/90 mmHg (2 measures, 4 hrs apart) in previously normotensive woman
○ No hypertension excludes condition
○ Can diagnose even if no proteinuria; systemic involvement, growth restriction
Features of HELLP syndrome
○ Haemolysis, elevated liver enzymes, low platelets
○ Affects 15% of those with pre-eclampsia though <1% of all pregnancies
○ Tends to occur between 27-37/40 though 15% present/progress post-partum
○ Average age is mid-20s but age > 35 is a risk factor
Summarise the mechanisms thought to underpin the development of preeclampsia/eclampsia.
- Abnormal changes in placental vasculature
○ Normally, foetal extra villous trophoblasts invade maternal decidua and replace smooth muscle and endothelial cells of spiral arteries
○ -> Hybrid, large calibre, foetomaternal vessels lacking SM
○ Vascular remodelling does not occur in pre-eclampsia
○ Failure to meet increased circulatory demands results in placental ischaemia- Endothelial dysfunction
○ Imbalance of proangiogenic and antiangiogenic factors produced by placenta
○ Markers of endothelial cell injury elevated in preeclampsia
§ Endothelin, cellular fibronectin, plasminogen activtor inhibiotr-1 - Normal placenta
- Endothelial dysfunction
What are the risk factors for pre-eclampsia/eclampsia
- Nulliparity
- Personal or family history of pre-eclampsia
- BMI > 30
- Age > 40
- Twin pregnancy
- Pre-existing conditions; diabetes, hypertension, cardiovascular, autoimmune, renal disease
Clinical features of pre-eclampsia
○ Modest to severe elevation of serum aminotransferases
○ Mild elevation of serum bilirubin
○ Coagulopathy in advanced/lethal disease
Morphological features of pre-eclampsia
○ Periportal sinusoids contain fibrin deposits
○ Haemorrhage into space of Disse
○ -> periportal hepatocellular coagulative necrosis
○ -> hepatic haematoma
○ Dissection of blood under Glisson capsule may lead to catastrophic hepatic rupture in eclampsia
○ Placental changes reflect vascular injury and ischaemic change:
○ Infarcts – can be large and numerous
○ Ischaemic change – particularly around villi
○ Retroplacental haematomas – uteroplacental vessels are prone to bleed
○ Decidual vessels can contain thrombi, fibrinoid necrosis, intimal lipid deposition (acute atherosis)
○ General pattern is fibrin thrombi and haemorrhage
○ Liver – irregular subcapsular and intraparenchymal haemorrhages
○ Kidneys – fibrin in glomeruli with swelling of cells. Can cause bilateral renal cortical necrosis if widespread and severe
○ Brain – foci of haemorrhage, small-vessel thromboses
○ Similar changes can sometimes be seen in heart, anterior pituitary gland
Complications of pre-eclampsia
- Main causes of mortality are stroke and pulmonary oedema
- Foetal growth restriction is present in 30%
- Risk of progression to severe pre-eclampsia/eclampsia
- But also a risk (mainly to foetus) with immediate delivery
- Increased risk of placental abruption
- Also a risk of still birth, renal failure
Summarise the hypotheses thought to involved in the development of HELLP.
- Variant of preeclampsia
○ Defective placental vascular remodelling during weeks 16-22 of pregnancy
○ Second wave of trophoblastic invade inadequate for placental perfusion
○ Hypoxic placenta releases various placental factors such as soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) which binds to vascular endothelial growth factor (VEGF) and placental growth factor (PGF)
○ Endothelial cell and placental dysfunction
○ Activation of coagulation cascade causes consumption of platelets
○ Macroangiopathic haemolysis- Acute maternal immune rejection
○ Immunocompetent maternal cells contact with genetically distinct foetus
○ Endothelial dysfunction, platelet activation and aggregation and arterial hypertension - Inborn errors of fatty acid oxidative metabolism
○ Cause liver damage secondary to insufficient mitochondrial oxidation of fatty acids required for ketogenesis
- Acute maternal immune rejection
What features in the history may raise suspicion for HELLP?
- Headache
- Nausea and vomiting
- Malaise
- RUQ or epigastric pain
- Visual disturbance
- Oedema
- Hypertension and proteinuria
- Unexplained thrombocytopenia
Complications of HELLP
○ DIC ○ Placental abruption ○ AKI ○ Pulmonary oedema ○ Liver haematoma - Mortality rate 1-2%
Morphological features of HELLP
Periportal haemorrhage and necrosis
Fibrin and hyaline deposits in hepatic sinusoids
Hepatic haematoma
Define amniotic fluid embolism.
- Amniotic fluid or foetal material enters mothers bloodstream
- Either clinical or post-mortem diagnosis
○ Clinical
§ Acute hypotension
§ Cardiac arrest
§ Acute hypoxia
§ Coagulopathy
§ In absence of other potential explanation
○ Post-mortem
§ Presence of foetal cells or materials in maternal blood vessels in lungs
- Either clinical or post-mortem diagnosis
Why is amniotic fluid embolism difficult to diagnose
- Sudden onset
- Diagnosis of exclusion
- Clinical diagnosis - no diagnostic tests
- Multiple differentials
- High maternal and foetal mortality
Pathophysiology of amniotic fluid embolism
- Entry of amniotic fluid or foetal tissue into maternal circulation
- Systemic inflammatory response
- Activation of coagulation factors
- Components of innate immune system
- Release of vasoactive substances
- Not mechanical obstruction of vessels
Risk factors of amniotic fluid embolism
○ Personal § Hx of allergies § Hx of cerebrovascular and cardiac disease § Advanced maternal age ○ Obstetric factors § Multiparty § Male foetus ○ Obstetric complications § Abruption of placenta § Placenta praevia § Cervical laceration § Uterine rupture ○ Labour factors § Trauma § Medical induction § Caesarean or operative vaginal delivery
