S UDDEN M ATERNAL C OLLAPSE Max Brinsmead PhD FRANZCOG July 2011.
FROM “THE” PATIENT TO PRE-EMPT: A JOURNEY FROM THE INDIVIDUAL TO GLOBAL HEALTH Peter von...
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Transcript of FROM “THE” PATIENT TO PRE-EMPT: A JOURNEY FROM THE INDIVIDUAL TO GLOBAL HEALTH Peter von...
FROM “THE” PATIENT TO PRE-EMPT: A JOURNEY FROM THE INDIVIDUAL TO
GLOBAL HEALTH
Peter von DadelszenBMedSc, MBChB, DipObst, DPhil, FRANZCOG, FRCSC, FRCOG
Professor and Academic Head of Obstetrics & Gynaecology, SGULHonorary Consultant in Obstetrics, SGFT
44th APOG Meeting, 4 December 2015
Disclosures
• I have been a paid consultant to Alere International and have received unrestricted grants-in-aid from them to support some of the research presented
• I own shares in LGT Medical
Objectives
• Describe the important milestones in my journey as a clinician-scientist
• Primarily related to pre-eclampsia
Milestones
• Look at the big picture v1.1
Pre-eclampsiamore than hypertension and proteinuria
pre-eclampsia
pulmonary oedema
DIC/abruption
hypertension
strokeeclampsia
proteinuria
acute renal failure
Pre-eclampsiaglobal burden
• Pre-eclampsia and the other HDP cause– IHME states 30,000 maternal deaths annually
Kassebaum et al. Lancet 2014
– However, field data from Pakistan imply that 40% of 40,000 PPH deaths are attributable to pre-eclampsia upon review
– Therefore, ≈46,000 maternal deaths annually• At least one woman every 7 minutes
– >500,000 perinatal deaths annually– ≈1500 deaths/d = 4 x A340s crashing daily
• However, no word for “pre-eclampsia” in Sindhi, Yoruba, Changana, Kannada …
• >99% of pre-eclampsia-related deaths occur in LMICs– Delays in triage, transport & treatment
• ≈50% of pre-eclampsia-related deaths occur in the home
Pre-eclampsiamore than hypertension and proteinuria
pre-eclampsia
pulmonary oedema
DIC/abruption
hypertension
strokeeclampsia
proteinuria
acute renal failure
Pre-eclampsia as PPH
Pre-eclampsiaglobal burden
• Pre-eclampsia and the other HDP cause– IHME states 30,000 maternal deaths annually
Kassebaum et al. Lancet 2014
– However, field data from Pakistan imply that 40% of 40,000 PPH deaths are attributable to pre-eclampsia upon review
– Therefore, ≈46,000 maternal deaths annually• At least one woman every 7 minutes
– >500,000 perinatal deaths annually– ≈1500 deaths/d = 4 x A340s crashing daily
• However, no word for “pre-eclampsia” in Sindhi, Yoruba, Changana, Kannada …
• >99% of pre-eclampsia-related deaths occur in LMICs– Delays in triage, transport & treatment
• ≈50% of pre-eclampsia-related deaths occur in the home
Population-level incidence of HDPCLIP Trials
Mozambique: Delivered women with hypertension: 70/964 (7.3%) Delivered women with proteinuric hypertension: 8/964 (0.8%)
GA at HDP recognitionCLIP Trials
GA at HDP recognitionCLIP Trials
Mozambique: Completed pregnancies reporting severe hypertension: 20/964 (2.1%)
Milestones
• Look at the big picture v1.1• Look at the big picture v1.2
Data from CEMD ,UK
Maternal death from pre-eclampsiaby diagnosis – UK; 1952 – 2008
Num
ber o
f mat
erna
l dea
ths/
trie
nniu
m
Data from CEMD ,UK
Maternal death from pre-eclampsiaby diagnosis – UK; 1952 – 2008
Num
ber o
f mat
erna
l dea
ths/
trie
nniu
m
Antihypertensives Magnesium
Data from CEMD ,UK
Maternal death from pre-eclampsiaby diagnosis – UK; 1952 – 2008
Num
ber o
f mat
erna
l dea
ths/
trie
nniu
m
Antihypertensives Magnesium
Surveillance,Timed delivery &
Reproductive choice
Milestones
• Look at the big picture v1.1• Look at the big picture v1.2• Look at the big picture v1.3
cardiorespiratory•hypertension•ARDS•pulmonary oedema•cardiomyopathy / LV dysfunction•intravascular volume constriction•generalised oedema
CNS•eclampsia•TIA / RIND / CVA•PRES
renal•glomerular endotheliosis•proteinuria•ATN•ARF
hepatic•periportal inflammation•hepatic dysfunction / failure•hepatic haematoma / rupture
haematological•microangiopathic haemolysis•thrombocytopoenia•DIC
placental IUGR(± maternal syndrome)
endothelial cell activation
intervillous souppre-eclampsia-specific shared with IUGR•placental debris •angiogenic imbalance•innate immune activation•oxidative stress•eicosanoids•cytokines
uteroplacental mismatch
decidual immune cell -
EVT interactions(invasion &
uteroplacental artery remodelling)inadequate placentation
(early-onset pre-eclampsia)genetic factors• familial risks • SNPs• epigenetics
lowered threshold• metabolic syndrome• chronic infection / inflammation• pre-existing hypertension• chronic renal disease / DbM• high altitude
maternal syndrome
normal placentation(late-onset pre-eclampsia)•macrosomia•multiple pregnancy•± lowered threshold
immunological factorsantigen exposure• primigravidity ( ) / primipaternity ( )• donor gamete(s) ( )• duration of cohabitation ( )• barrier contraception ( ) / fellatio ( )• prior miscarriage ( )• smoking ( )
Milestones
• Look at the big picture v1.1• Look at the big picture v1.2• Look at the big picture v1.3• Your research is only as good as your controls
PLGF and IUGR vs constitutionally-small
• Preliminary data– Single site pilot study– Placental pathology to define placental IUGR
Benton et al. AJOG 2011
PLGF and IUGR vs constutionally-small
Gestational age at sampling (week)
Pla
ce
nta
l gro
wth
fa
cto
r (p
g/m
L)
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 4010
100
1000
10000 Grade 0Grade 1Grade 2Grade 3
Constitutionally-small
Placental IUGR
Benton et al. submitted
STRIDER consortium of RCTssildenafil 25mg tid
NZ & AusHRC (NZ)
Netherlands(ZonMW)
UK(MRC)
ROI(HRB)
Canada(CIHR)
STRIDER
cardiorespiratory•hypertension•ARDS•pulmonary oedema•cardiomyopathy / LV dysfunction•intravascular volume constriction•generalised oedema
CNS•eclampsia•TIA / RIND / CVA•PRES
renal•glomerular endotheliosis•proteinuria•ATN•ARF
hepatic•periportal inflammation•hepatic dysfunction / failure•hepatic haematoma / rupture
haematological•microangiopathic haemolysis•thrombocytopoenia•DIC
placental IUGR(± maternal syndrome)
endothelial cell activation
intervillous souppre-eclampsia-specific shared with IUGR•placental debris •angiogenic imbalance•innate immune activation•oxidative stress•eicosanoids•cytokines
uteroplacental mismatch
decidual immune cell -
EVT interactions(invasion &
uteroplacental artery remodelling)inadequate placentation
(early-onset pre-eclampsia)genetic factors• familial risks • SNPs• epigenetics
lowered threshold• metabolic syndrome• chronic infection / inflammation• pre-existing hypertension• chronic renal disease / DbM• high altitude
maternal syndrome
normal placentation(late-onset pre-eclampsia)•macrosomia•multiple pregnancy•± lowered threshold
immunological factorsantigen exposure• primigravidity ( ) / primipaternity ( )• donor gamete(s) ( )• duration of cohabitation ( )• barrier contraception ( ) / fellatio ( )• prior miscarriage ( )• smoking ( )
Milestones
• Look at the big picture v1.1• Look at the big picture v1.2• Look at the big picture v1.3• Your research is only as good as your controls• Tell a story
cardiorespiratory•hypertension•ARDS•pulmonary oedema•cardiomyopathy / LV dysfunction•intravascular volume constriction•generalised oedema
CNS•eclampsia•TIA / RIND / CVA•PRES
renal•glomerular endotheliosis•proteinuria•ATN•ARF
hepatic•periportal inflammation•hepatic dysfunction / failure•hepatic haematoma / rupture
haematological•microangiopathic haemolysis•thrombocytopoenia•DIC
placental IUGR(± maternal syndrome)
endothelial cell activation
intervillous souppre-eclampsia-specific shared with IUGR•placental debris •angiogenic imbalance•innate immune activation•oxidative stress•eicosanoids•cytokines
uteroplacental mismatch
decidual immune cell -
EVT interactions(invasion &
uteroplacental artery remodelling)inadequate placentation
(early-onset pre-eclampsia)genetic factors• familial risks • SNPs• epigenetics
lowered threshold• metabolic syndrome• chronic infection / inflammation• pre-existing hypertension• chronic renal disease / DbM• high altitude
maternal syndrome
normal placentation(late-onset pre-eclampsia)•macrosomia•multiple pregnancy•± lowered threshold
immunological factorsantigen exposure• primigravidity ( ) / primipaternity ( )• donor gamete(s) ( )• duration of cohabitation ( )• barrier contraception ( ) / fellatio ( )• prior miscarriage ( )• smoking ( )
fullPIERS sites2023 women
Christchurch
Perth
Nottingham
LeedsKingstonOttawa
Sherbrooke
VancouverRichmond
SurreyCranbrook
von Dadelszen et al. Lancet 2011
Payne et al. PLoS Med 2014
home-based (± transfer to PHC)
or PHC-based assessment &
initial management
App-guided CLIP package of care (≥1 trigger) 750mg methyldopa po (only if sBP ≥160; not repeated in PHC)10g MgSO4 im (if sBP ≥160, eclampsia, miniPIERS p ≥25%, pv bleeding + sBP≥140; not repeated in PHC)urgent transport (if sBP ≥160, eclampsia, coma, stroke, miniPIERS p ≥25%, pv bleeding, ++++ protein, no FM ≥12h)
App-guided CLIP triggers to OVERCOMINGinitiate community interventions THE 3 DELAYSminiPIERS p ≥25% Triage/Transport/TreatmentsBP ≥160 Triage/Transport/Treatmenteclampsia Triage/Transport/Treatmentpv bleeding (presumed abruption) Triage/Transport/Treatment++++ proteinuria Triage/Transport/Treatmentabsent fetal movements ≥12h Triage/Transport/Treatment
community engagement
& cHCP education
urgent transport (<4h)(if: miniPIERS p ≥25%, sBP ≥160, stroke, coma, eclampsia, pv bleeding, +
+++ protein, absent FM ≥12h)
non-urgent transport (<24h) (if: miniPIERS p <25%, sBP 140-159mmHg, <++++ protein)
facility capacity enhancement
CME/CPDM&M reviews
CEmOC facility for definitive care
ongoing BP controlongoing MgSO4
delivery – IOL vs C/Snewborn care
community engagement
& cHCP education
urgent transport (<4h)(if: miniPIERS p ≥25%, sBP ≥160, stroke, coma, eclampsia, pv bleeding, +
+++ protein, absent FM ≥12h)
non-urgent transport (<24h) (if: miniPIERS p <25%, sBP 140-159mmHg, <++++ protein)
facility capacity enhancement
CME/CPDM&M reviews
home-based (± transfer to PHC)
or PHC-based assessment &
initial management
App-guided CLIP package of care (≥1 trigger) 750mg methyldopa po (only if sBP ≥160, dBP ≥110; not repeated in PHC)10g MgSO4 im (if sBP ≥160, dBP ≥110, eclampsia, miniPIERS p ≥25%, pv bleeding + sBP≥140; not repeated in PHC)urgent transport (if sBP ≥160, dBP ≥110, SI ≥1.7, eclampsia, coma, stroke, miniPIERS p ≥25%, pv bleeding, ++++ protein, no FM ≥12h)
App-guided CLIP triggers to OVERCOMINGinitiate community interventions THE 3 DELAYSminiPIERS p ≥25% Triage/Transport/TreatmentsBP ≥160 Triage/Transport/TreatmentdBP ≥110 Triage/Transport/TreatmentSI ≥1.7 Triage/Transport/Treatmenteclampsia Triage/Transport/Treatmentpv bleeding (presumed abruption) Triage/Transport/Treatment++++ proteinuria Triage/Transport/Treatmentabsent fetal movements ≥12h Triage/Transport/Treatment
CEmOC facility for definitive care
ongoing BP controlongoing MgSO4
delivery – IOL vs C/Snewborn care
Payne et al. JOGC 2015
• additional 20% of women who will suffer adverse outcome identified• increased from 65% to 85%
Payne et al. JOGC 2015
community engagement
& cHCP education
urgent transport (<4h)(if: miniPIERS p ≥25%, sBP ≥160, stroke, coma, eclampsia, pv bleeding, +
+++ protein, absent FM ≥12h)
non-urgent transport (<24h) (if: miniPIERS p <25%, sBP 140-159mmHg, <++++ protein)
facility capacity enhancement
CME/CPDM&M reviews
home-based (± transfer to PHC)
or PHC-based assessment &
initial management
App-guided CLIP package of care (≥1 trigger) 750mg methyldopa po (if sBP ≥160; not repeated in PHC)10g MgSO4 im (if sBP ≥160, eclampsia, miniPIERS p ≥25%, pv bleeding + sBP≥140; not repeated in PHC)urgent transport (if sBP ≥160, SpO2 <93%, eclampsia, coma, stroke, miniPIERS p ≥25%, pv bleeding, ++++ protein, no FM ≥12h)
App-guided CLIP triggers to OVERCOMINGinitiate community interventions THE 3 DELAYSminiPIERS p ≥25% Triage/Transport/TreatmentsBP ≥160 Triage/Transport/TreatmentSpO2 <93% Triage/Transport/Treatmenteclampsia Triage/Transport/Treatmentpv bleeding (presumed abruption) Triage/Transport/Treatment++++ proteinuria Triage/Transport/Treatmentabsent fetal movements ≥12h Triage/Transport/Treatment
CEmOC facility for definitive care
ongoing BP controlongoing MgSO4
delivery – IOL vs C/Snewborn care
cardiorespiratory•hypertension•ARDS•pulmonary oedema•cardiomyopathy / LV dysfunction•intravascular volume constriction•generalised oedema
CNS•eclampsia•TIA / RIND / CVA•PRES
renal•glomerular endotheliosis•proteinuria•ATN•ARF
hepatic•periportal inflammation•hepatic dysfunction / failure•hepatic haematoma / rupture
haematological•microangiopathic haemolysis•thrombocytopoenia•DIC
placental IUGR(± maternal syndrome)
endothelial cell activation
intervillous souppre-eclampsia-specific shared with IUGR•placental debris •angiogenic imbalance•innate immune activation•oxidative stress•eicosanoids•cytokines
uteroplacental mismatch
decidual immune cell -
EVT interactions(invasion &
uteroplacental artery remodelling)inadequate placentation
(early-onset pre-eclampsia)genetic factors• familial risks • SNPs• epigenetics
lowered threshold• metabolic syndrome• chronic infection / inflammation• pre-existing hypertension• chronic renal disease / DbM• high altitude
maternal syndrome
normal placentation(late-onset pre-eclampsia)•macrosomia•multiple pregnancy•± lowered threshold
immunological factorsantigen exposure• primigravidity ( ) / primipaternity ( )• donor gamete(s) ( )• duration of cohabitation ( )• barrier contraception ( ) / fellatio ( )• prior miscarriage ( )• smoking ( )
Milestones
• Look at the big picture v1.1• Look at the big picture v1.2• Look at the big picture v1.3 • Your research is only as good as your controls• Tell a story• And finally …
Marry well!