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Maternal Death – mainly UK issues���

Sebastian Lucas

Emeritus-Professor of Clinical Histopathology

King’s College London School of Medicine

Dept of Histopathology

St Thomas’ Hospital

London SE1, UK

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Fetuses …….time-bombs?

~140 million per annum

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​

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In UK: 700,000 pa

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Topics

  • Epidemiology & rates
    • UK vs global
  • What is a ‘maternal death’?
  • Why do they happen?

​

  • Can we reduce the rates further?

​

​

  • Contexts:
  • Physiological changes in pregnancy and at delivery
  • Susceptibility to infections in pregnancy
  • Rising prevalence of co-morbidities

The interaction of Obstetrics with general Medicine, Pathology & Politics

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Implantation

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Anatomic and physiological changes caused by pregnancy

  1. a state of relative thrombophilia during pregnancy VTE

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  • gravid uterus as SOL VTE

​

  • hormonal changes weaken connective tissue aorta rupture

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  • Increased susceptibility to infections controlled by cell-mediated immunity

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  • Cardiac arrhythmias [tbc]

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  • blood volume changes during gestation and delivery – strain on heart and lungs

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Maternal Death�Question 1

What is a maternal death?

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Definitions

Maternal

Death

during pregnancy-birth - 42 days post-delivery

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Direct

​

Disease directly due to being pregnant

​

​

eg eclampsia, AFE, uterine rupture, abortion, suicide

Indirect

​

Disease not directly due to pregnancy, but made worse by pregnancy

​

eg heart disease, pulmonary hypertension, [suicide], HbSS

Coincidental

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Disease or event unrelated to pregnancy and not influenced by pregnancy

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eg homicide, cancer, RTC, drug o/d

Late

Maternal

Death

43 -365 days post-delivery

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Maternal mortality

  • Globally, the disease with the greatest incidence rate differences [MDG-5]

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Maternal death�Question 2

How many?

Direct + Indirect causes

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Globally ~ 300,000 - 500,000 pa [conflicting data!]

UK ~ 75 pa

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Maternal Death rates

1. Direct + Indirect causes

    • as proportion of total live births (international)
    • as proportion of total maternities (UK)

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Maternal Mortality Rate

MMR = n/105 live births or maternities

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Maternal mortality rates:�did autopsy data cause the decline?

UK

USA

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Current UK

MMR = 11/100,000

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Maternal Death rates

  1. Direct + Indirect causes

= MMR n/105 live births or maternities

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2. Lifetime risk of maternal death for a 15yr old female

= 1/n

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LICs

1 in 7- 45

EUROPE

1 in 5,400

Overall

X100 risk ratio

Rich vs Poor counties

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Maternal death�Question 3

When do these deaths occur?

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When do women die?

  • UK 2018-2020

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  • 18% delivery day

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  • 18% <20 weeks gest
  • 10% >20 weeks
  • 54% post-natal

Bangladesh

Deaths per 1000 p-y

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Where and how?

In resource-poor countries

  • 2/3 die in health centre
  • 1/3 at home

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Hospital scenarios

  1. Arrive moribund
  2. Arrive with complications – but too late
  3. Deliver in hospital and develop complications
    • natural
    • iatrogenic

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Maternal Death�Question 4

Why do mothers die?

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UK Confidential Enquiries into Maternal Death: reports since 1950s

In depth peer reviews of deaths – annual now

Identify remediable factors to reduce future deaths

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Why study Maternal Death?

Tip of the iceberg

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Lessons from Near Misses

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Long-term morbidity

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MD

Maternal

Morbidity

X 15-20

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Global causes

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UK data 21st century�The commonest specific causes of MD

2003-5

  1. Cardiac disease
  2. Venous thrombo-embolism (VTE)
  3. Pre/eclampsia (hypertensive diseases)
  4. Psychiatric (suicide)
  5. Genital tract sepsis
  6. Amniotic fluid embolism

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2018-2020

  1. Psychiatric (suicide)
  2. Cardiac
  3. COVID-19
  4. VTE
  5. Neurological – SAH and SUDEP
  6. Sepsis
  7. Other Indirect
  8. Haemorrhage
  9. Early pregnancy
  10. AFE
  11. Pre-eclampsia
  12. Cancer
  13. Anaesthesia

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And now for the pathology

DIRECT

  • Peri-partum hge
  • Ectopic pregnancy
  • Eclampsia
  • Amniotic fluid embolism

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INDIRECT

  • VTE/PE
  • Cardio-vascular

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……and SEPSIS

http://www.rcpath.org/resources/pdf/g100autopsypracticesection5maternaldeathfinaloct2010.pdf

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Ectopic pregnancy – 1st & 2nd trimester pregnancy

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Ectopic & haemoperitoneum:�death from haemorrhagic shock

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Peri-partum haemorrhage

Accidental

  • Placental abruption

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  • Uterine rupture

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  • Post-partum bleeding
    • Uterine atony
    • Septic shock & DIC
    • AFE

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  • Trauma to lower uterus, cervix & vagina during delivery

Constitutional

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  • Placentation pathology

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    • Placenta praevia

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    • Placenta accreta

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    • Retained placenta

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Abruption of the placenta

BLOOD CLOT

PLACENTA

Remediable? No

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Abnormal placentation

Placenta praevia

Placenta accreta

Risk factor = previous CS

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Placenta percreta

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Retained placenta

  • Term vaginal delivery at home
    • Syntometrine given
  • 7 hours post-delivery
  • Collapse and PV bleeding++
  • To hospital
    • 1/3 of placenta removed from uterus
  • Died from bleeding despite emergency hysterectomy

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Rupture of uterus

  • Spontaneous
    • Previous Caesarean section scar
    • Obstructed labour

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  • Traumatic
    • Obstetric instrumentation

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  • Drug-induced
    • Medical induction of labour
    • Medical termination of pregnancy

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Previous CS – scar rupture

  • Uncommon

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  • Trial of labor

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  • Emergency CS if things go wrong

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..the ultimate obstructed labour

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Vaginal trauma and haemorrhage

  • Forceps delivery
  • Immediate catastrophic hge

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Died despite Tx etc

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Autopsy

  • Remove the whole genital tract en bloc
  • Fix in formalin
  • Serial transverse slice
  • Numerous tissue blocks
  • Search for the torn vessels

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Histology proves the site of laceration in vagina

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And now for the pathology

DIRECT

  • Peri-partum hge
  • Ectopic pregnancy
  • Eclampsia
  • Amniotic fluid embolism

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INDIRECT

  • VTE/PE
  • Cardio-vascular

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……and SEPSIS

http://www.rcpath.org/resources/pdf/g100autopsypracticesection5maternaldeathfinaloct2010.pdf

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Hypertensive diseases

  • Pre-existing condition [ = remediable]
    • Hypertension
    • Renal disease

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  • Developing during pregnancy
    • Pre-eclampsia = proteinuria, oedema, H/T

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    • Eclampsia = PET + fitting

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PET & eclampsia pathology

  • CNS
    • Intracerebral hamorrhage

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  • Liver
    • Haemorrhage
    • Necrosis

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  • Kidney
    • Glomerular capillary endotheliosis

​

​

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Presentation to death

  • Fitting
  • Sudden collapse - cardiac
  • Intracerebral haemorrhage
  • Liver and renal failure

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Brain – eclampsia & haemorrhage

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Liver eclampsia

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PET kidney – bloodless glomerular endotheliosis

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Amniotic fluid embolism (AFE)�a typical scenario

  • F 39yr
  • Three children A&W
  • Fourth pregnancy, delivery @41 weeks
  • Vaginal delivery
  • As baby head crowns, collapse & becomes unresponsive
  • Develops uterine bleeding, necessitating hysterectomy
  • Dies hours later, never recovering consciousness

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Autopsy: lung arteriole

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IHC – fetal squames in amniotic fluid

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AFE

  • Risk factors
  • Medical induction of labour
  • Caesarian section
  • Forceps and vacuum delivery

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  • Higher maternal age
  • Diabetes
  • Polyhydramnios
  • Eclampsia
  • Cervical laceration
  • Placenta previa and abruption

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  • But most just happen out the blue

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  • Pathogenesis

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Cardiac &

respiratory

arrest

Acute

anaphylactoid

shock

Bleeding

coagulopathy

(DIC)

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AFE in Canada 1991-2002

Rate per 100,000

Clinical Incidence = 6/100,000

Mortality = 0.8/100,000 =~20%

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UK maternal autopsy data

  • 68% overall have an autopsy (cf 14% of all deaths in E&W)

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  • Direct MD – 86%
  • Indirect MD – 75%
  • Coincidental – 56%

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  • 6 week to 1 year pp – 59%

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Main points

1. high autopsy rate

2. uncommon; most path-ologists will not encounter a case

3. should be performed in expert centres

5. ALL MD autopsy reports

will be scrutinised by coroners, family, lawyers, & MBRRACE – and bad autopsies highlighted

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Venous thrombo-embolism

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Pulmonary thromboembolism

  • Pre-delivery 1/3

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  • Puerperium 2/3
    • days to weeks

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Source: pelvic veins

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F27yr; 27/40 gestation.�One ‘fainting’ episode.�Next morning: found dead at home

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Pregnancy risk factor for VTE

  • Pregnant uterus

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  • Presses on left iliac vein

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  • Fibroids makes this worse

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  • Obesity

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  • Caesar section & immobility

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VTE and pregnancy

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  • Thrombophilia?
    • Antiphospholipid syndrome
    • Factor V Leiden
    • Protein C & S deficiency
    • Prothrombin gene variant
    • Thrombocythaemia

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  • What can you do on post- and pre-mortem samples? Nothing.
  • Basic risk of VTE in women = 10/105pa

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  • During pregnancy risk = 100/105

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  • ie x10 risk in pregnancy

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VTE – what we can do

  • Confirm the VTE with histology
  • Estimate chronology of VTE from gross and histopathology
  • Adherent clot in PAs and leg veins?
  • Organisation at clot/intima interface

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  • If chronic VTE, should clinicians have identified this and initiated prophylactic anticoagulation?

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Cardiac death in UK

Clinical pathology

% cases

Myocardial disease

25%

LVH, myocarditis, PPCM, HCM, DCM, NOS

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Ischaemic heart disease

20%

Atherosclerosis, coronary artery dissection

​

SADS/MNH

18%

Valvular disease

13%

Rheumatic, congenital, endocarditis.

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Other cardiovascular

  • Aortic dissection 11%

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  • Pulmonary hypertension
  • Congenital heart
  • Undetermined

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Aortic dissection (& Marfan’s)

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Risk factor analysis:�the swiss cheese model

Inherited weakness of aorta media

+ progresterone effect on smooth muscle

+/- hypertension

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Puerperal cardiomyopathy (PPCM)

  • Cardiac failure
    • between one month pre-delivery & 5 months post-delivery
    • other causes excluded

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  • A dilated cardiomyopathy

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  • Very complex endocrine (progesterone) pathogenesis, with an inherited component

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SADS – an emerging problem�many are inheritable syndromes

  • Sudden unexpected arrhythmic death syndrome
  • Peri- and post-partum
  • ALL other causes of death excluded
  • Morphologically normal heart (MNH)

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  • Stress of pregnancy & delivery
  • Underlying electrical instability
    • long QT etc

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SADS with morphologically normal heart

  • Channelopathies
  • Ion channel disorders

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    • Long QT syndrome
    • Short QT syndrome
    • Brugada syndrome
    • Catecholaminergic polymorphous ventricular tachycardia
    • Lev-Lenegre disease
    • etc
  • Familial bradycardia
    • Lamin A/C disease
    • Dsytrophinopathies
    • Mutation of gamma subunit of the adenosine monophosphate activated protein kinase (PRKAG2)
    • Holt-Oram syndrome
    • etc

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Long QT and pregnancy

  • Pre-pregnancy risk of cardiac event = 1

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  • During pregnancy = 0.28 (0.1-0.76)

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  • First 9 months post-partum = 2.7 (1.8-4.3)

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  • Post-post-partum = 0.91

Seth et al,

J Am Coll Cardiol 2007, 49:1092-8

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And now for the pathology

DIRECT

  • Peri-partum hge
  • Ectopic pregnancy
  • Eclampsia
  • Amniotic fluid embolism

​

INDIRECT

  • VTE/PE
  • Cardio-vascular

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……and SEPSIS

http://www.rcpath.org/resources/pdf/g100autopsypracticesection5maternaldeathfinaloct2010.pdf

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Died 24 hours post delivery�Group A Streptococcus pyogenes

Streptococcal

toxic shock.

‘Scarlet fever’ rash

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Sepsis – GAS endomyometritis

Gram+ cocci

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Multiple routes of infection

Mother Vagina

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Genital tract

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Endomyometritis

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(Chorio-amnionitis)

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HCW

Other person

(community, children)

Mother nasopharynx

Mother blood

Septicaemia

SIRS

Skin lesion (eg breast)

Mother

perineum

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Ascending infection

  • 2nd trimester
    • Rupture of membranes
    • GT sepsis

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  • 3rd trimester
    • Post-delivery
    • Traumatised tissues
    • Ascending infection

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How genital tract sepsis happens?

BLOOD

?

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Other infection scenarios� - all linked by CMI of pregnancy

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  • Pneumoccocal meningitis
  • Listeriosis [cheese]
  • Tuberculosis
    • [HIV in Africa – very bad]
    • In UK, Asian immigrants
  • Herpes viruses

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Fatal STI case

Mother

  • 25 yr old, primip, HIV-ve
  • 41 weeks pregnant
  • Induced
  • Chorioamnionitis
  • Emergency CS
  • Well........then
  • D5: abdo pain, unwell
  • D9: in ITU with liver failure
  • Liver Bx – HSV+ necrosis
  • D10: died of multi-organ failure

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Baby

  • Apgar 10 @ 10
  • IV antibiotics - stopped
  • D7: fever
  • D10: septic screen
    • CSF – HSV+ve PCR
  • Diag: HSV encephalitis
  • Acyclovir

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  • Now OK

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Case

  • Autopsy
  • Necrotic cervix & uterus

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  • Liver necrotic

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  • Above the diaphragm: no infection
  • Histology

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  • HSV & necrosis
    • HSV type 2

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Cx - HSV2

Normal placenta

Necrotic cervix

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Lots of rare causes of MD

  • Thrombotic thrombocytopaenic purpura
  • Uterine vein varix and VTE
  • Adrenal phaeochromocytoma
  • Behcet’s disease
  • HIV (pneumocystosis)
  • Splenic artery aneurysm rupture
  • Ogilvie syndrome
  • Benign metastasising leiomyoma
  • General anaesthesia complications

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Co-morbidities in UK pregnant women

  • INCREASING AGE
  • Obesity, Diabetes & Hypertension
  • Coronary & valvular heart disease
  • Congenital heart disease
  • Chronic liver disease
  • Chronic kidney disease
  • Chronic rheumatic disorders (SLE)
  • Chronic lung diseases (pulm hypertension)
  • Cancer and chemotherapies
  • IBD and chemotherapies
  • All reasons why Indirect maternal deaths are increasingly common

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  • Fact: pregnant women are not generally receptive of to advice over pregnancy risk

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Obesity – many problems

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Broader: UK risk factors for MD

MEDICAL

  • AGE
  • Late booking & poor antenatal attendance
  • Obesity & co-morbidities
  • Diabetes
  • Not IVF

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SOCIAL

  • Age – bi-modal
  • Social-economic status:
    • unemployed, no partner
  • Ethnicity – Black african
  • Asylum seekers, refugees
  • Travellers
  • Domestic violence
  • Substance abuse

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Why MD matters in UK

  • Only <100 deaths a year?
  • Focuses attention on maternity care
  • Most families want to know what happened
  • MBRRACE audit and accurate data
  • Maternity units are monitored
    • Northwick Park Hospital maternity shut temporarily in 2006
  • Remediable factors identified
  • Potential familial diseases identified
    • Thrombophilia
    • Aortic dissection
    • Cardiovascular disease
      • Cardiomyopathy, SADS

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Conclusion

  • Many easy clinical pathologies in MD

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  • BUT

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  • Most difficult cases: sudden unexpected death at time of delivery, despite consultants around, CPR & ITU

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Sudden cardio-respiratory collapse �peri-delivery

Cardio-

pulmonary

collapse

Haemorrhage

Amniotic

fluid

embolism

Cardiac

SADS

Pulmonary

thrombo-

embolism

Air

embolism

Anaesthesia

- regional

- general

Sepsis

Eclampsia

Acute

anaphylaxis

Undetermined

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Conclusion

  • Many easy clinical pathologies in MD

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  • Most difficult cases: sudden unexpected death at time of delivery
  • You really do not want to be doing these autopsies on your own for the first time
  • Advice is available: RCPath Guideline
  • Expert centres the best scenario