Medical Problems in
Pregnancy
Dr Suzy Matts FRCOG
Consultant Obstetrics and Gynaecology
George Eliot Hospital
Introduction
• Most women in pregnancy are healthy
• However, those with medical disorders require expert
care
• Care may be by the obstetrician, +/- GP and/or medical
specialist
• May be through normal or specialised ANC
• Most complex disorders may need multidisciplinary
antenatal care in a tertiary centre
Medical Disorders
• What disorders can you think of that can affect
pregnancy?
Medical Disorders
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Asthma
Cystic fibrosis
Hypertension/PIH/PET
Arrthymias
Valvular disease
Cardiomyopathy
Cyanotic heart disease
VSD/ASD
Pulmonary hypertension
Epilepsy
Multiple sclerosis
Intracranial hypertension
Benign cranial tumours eg pit
adenomas
• Obstetric Cholestasis
•
•
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Acute Fatty Liver of Pregnancy
IBS
Crohns/Ulceative colitis
Thrombophilias
VTE
Antiphospholipid syndrome
SLE
Rheumatoid arthritis
Sickle cell
disease/thalassaemias
Anaemia
Diabetes
Hypo/hyperthyroidism
Adrenal disease
Cancer
Background
• Medical disorders can impact on
pregnancy in two ways
– Disorders caused by the pregnancy eg
• PET/PIH
• VTE
– Disorders pre-existing by exacerbated by the
effects of the pregnancy eg
•
•
•
•
Heart disease
Asthma
Immune disorders
Epilepsy
These conditions make major
contributions to maternal deaths
Condition
2003-5
2000-2
1997-9
Thromboembolism
41
30
35
Pre-eclampsia and
eclampsia
18
14
16
Cardiac Disease
48
44
35
Epilepsy
11
13
9
Asthma
4
5
5
Diabetes Mellitus
1
3
4
Total-named
diseases
123 (42%)
109 (42%)
104 (43%)
TOTAL
Direct + Indirect
295
261
242
Exercise-15 minutes
• Prepregnancy
actions/changes/ issues
• Antenatal issues
– Effects on mum
– Effects on baby
• Screening
• Medication issues
• Contraindications
• Delivery issues
• Postnatal issues
• Neonatal issues
GROUPS:
• ASTHMA
• EPILEPSY
• DIABETES
• ESSENTIAL HYPERTENSION
• THROMBOPHILIA eg PROTEIN
C DEFICIENCY and APLS
DIABETES
• Important issue in pregnancy
– Major impacts on maternal and fetal health
• Requires multidisciplinary care in combined
clinic
• Pre-existing Type 1
• Pre-existing Type 2 (increasing)
• Gestational Diabetes (increasing)
Diabetes Mellitus and Pregnancy-1
• Diabetes mellitus affects all systems in the
body-actual or effective insulin deficiency
• 3-4 per 1000 pregnancies
• Before insulin in 1921, 40% women died
during pregnancy (usually DKA)
• Remainder died within 2 years of delivery
• Fetal loss rate >50%
Diabetes Mellitus and Pregnancy-2
•
•
•
•
•
•
•
Introduction of insulin improved outcome
Maternal mortality fell to 2-3%
Now deaths very rare
Fetal loss rates remained high
Initially concentrated on reducing stillbirth but PNMR high
1970s-effect on fetus of abnormal glucose levels
Optimisation of maternal control and fetal surveillance
should lead to PNMR close to non-diabetic
– Recent studies show PNMR still double non-diabetic
– Fetal anomaly rates 4x those of non-diabetic
• Effects of diabetes on
pregnancy
– Miscarriage
– Fetal malformations
• Cardiac
• Neural tube
• Caudal regressions
syndrome (200x↑)
–
–
–
–
IUGR
Macrosomia
Unexplained IUD
PET
• Effects of pregnancy on
diabetes
– Poorer control
– Deterioration of renal
function
– Deterioration of
opthalmic disease
– Gestational DM
Effects of Diabetes - fetus
Maternal diabetes
hyperglycaemia
Fetal hyperinsulinaemia
Increased fetal growth
Fetal
macrosomia
Polyuria
Polyhydramnios
Increased oxygen demands
Polycythaemia
Risk of
cerebral palsy
Risk of preterm labour
/ malpresentation/
cord prolapse
Risk of birth injury/
shoulder dystocia
Neonatal
hypoglycaemia
Risk of unexplained
term stillbirth
Fetal effects
• Macrosomia
– Increased risks of birth injury/ shoulder
dystocia***
– Major cause of obstetric litigation
– LSCS recommended in DM where
macrosomia and EFW >4000g
• Polyhdramnios
– Fetal malpresentations and possible increased
risk preterm labour
• Hyperinsulinaemia
– Severe hypoglycaemia (risk of CP)
• Polycythaemia
– Thrombotic effects
– Jaundice
• Hypocalcaemia
• HOCM
Perinatal mortality by plasma glucose levels
Pregnancy is diabetogenic
• Fetus has little capacity for gluconeogenesis
– enzymes are deactivated by low oxygen tensions
• Glucose obtained from maternal blood
– therefore dependent on maternal nutritional status
• Maternal endocrine controls designed to keep blood
glucose levels within tight limits
– Insulin secretion prevents hyperglycaemia by increasing glucose utilisation for
glycogen and fat synthesis and storage
– Gut absorption and gluconeogenesis prevent hypoglycaemia
Pregnancy is diabetogenic
• Progesterone increases maternal appetite and stimulates
deposition of glucose in fat stores
– Also increases renal gluconeogenesis
– Increased protein catabolism
• Human placental lactogen (hPL, hPS) acts like growth
hormone (GH)
–
–
–
–
Placental variant of GH
Polypeptide hormone
Produced from end of 1st trimester onwards
Mobilises fatty acids for maternal metabolism
Pregnancy is diabetogenic
• Relative insulin insensitivity in later pregnancy
– Effects of hPL- exaggerated rate and amount of insulin release due
to relative insulin insensitivity (requirements may increase by
~30%)
– Reduced insulin sensitivity also due to effects of increased levels of
cortisol, oestrogen and progesterone
– Prolonged hyperglycaemia after eating
– Reduced uptake of glucose by maternal tissues more by
placental uptake
– Facilitated diffusion only saturated at maternal levels of 20 mmol/l
Gestational diabetes
• Development of severe glucose intolerance in pregnancymay require insulin treatment
• ADA recommends all women should have 50g OGTT 24-28
weeks
• UK-women with specific risk factors screened – 75g OGTT
• Limit to <32 weeks due to slower gastric emptying and
unpalatability in late pregnancy
• Alternatives: HbA1C, blood glucose series
Risk factors for GDM
• Family history
– One first degree relative
– Two second degree relatives
• Poor obstetric history
– Esp. death of previous macrosomic baby
•
•
•
•
•
•
Significant glycosuria
Polyhydramnios
Macrosomic infant in this pregnancy
Polycystic ovary syndrome
Wt >100kg or BMI >30
South Asian, Middle Eastern or African origin
Oral glucose tolerance test-interpretation
(WHO) **=diagnostic of GDM
75g
•
OGTT
Normal
Impaired
Diabetes
Fasting
mmol/l
<6.0
<6.0
<6.0 or
≥6.0**
2 hours
mmol/l
≤7.8
7.8-11.0
>11.0**
Diabetes and Pregnancy-Key Points
• Pregnancy is diabetogenic, worsening preexisting diabetes and precipitating
gestational DM
• Increasing obesity increases incidence
gestational and Type 2 DM
• Poorer control worsens fetal and maternal
outcomes
• Hyperglycaemia is associated with acute
fetal demise: hypoglycaemia is associated
with cerebral palsy
Diabetes Antenatal Combined Clinic
• One stop clinic for women with diabetes in
pregnancy-all consultant units
• See all professionals on one visit-may or may not
be in same room, depending on size of clinic!
•
•
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Obstetrician
Diabetes physician
Diabetes nurse
Diabetes specialist midwife
Sonographers
Dietician
(psychologist)
Management
• Pre-pregnancy
– Optimise control-aim for BM 4-7
– HbA1C 6.0% or less
– High dose folic acid 5mg/day
– Stop smoking, weight reduction of BMI raised
• Early Pregnancy
– Early booking at 6 weeks
– Combined clinic every 1-2 weeks
– Early dating/viability scan
Management
• Screening
• Combined test at 12 weeks (sl lower sensitivity in DM)
– Detailed USS including extended cardiac views
• Diabetic control
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–
–
–
–
May need diet, oral HG or insulin
Aim for BM 4-7
Keep HbA1C <6.0%
Retinal screening every trimester
Dietetic support
Management
• Pregnancy Care
– Regular antenatal care
– Serial growth scans 28. 32. 36 weeks
– Monitoring for PET
– Fetal wellbeing monitoring from 34 weeks
– Elective delivery IOL or LSCS
• 38-39 weeks in pre-existing DM
• 38 wks in GDM on insulin, may be 41 weeks if GDM on
diet with normal BMs and fetal growth
Management
• Neonatal
– Paediatric alert
– Neonatal surveillance at delivery-may be with mother
– Monitor BMs to ensure no neonatal hypoglycaemia
• Postnatal
– Pre-Existing: Return to prepregnancy insulin / oral HG
agent regime
– GDM: stop treatment and monitor BMs for 48 hours
to ensure return to normal and no persistence of IGT
Thyroid and Pregnancy
• hCG has thyrotrophic function
– May suppress TSH during first trimester
– Thyrotoxicosis may be a feature of hydatidiform pregnancy where
levels of hCG are extremely elevated
• Thyroid function remains essentially normal in pregnancy
– Marked increase in thyroid binding globulin (? Effect of oestrogen?)
– Increase in bound thyroxin (T4) t3 (more active)and rT3 (inactive)
– Free T4 and T3 are unaltered or slightly reduced
• NOTE: increased BMR, tachycardia, elevated body temperature
and increased CO are normal in pregnancy but may mimic the
effects of hyperthyoidism
Thyroid and Pregnancy
• Hypothyroid:
– Check TFT (TSH) at booking and every trimester
– Likely to need increase in thyroxine dose during
pregnancy
– If anti-thyroid antibodies, inform paeds who will
need to check fetal TFT at birth
Thyroid and Pregnancy
• Hyperthyroid
–
–
–
–
May worsen due to HCG
Risks-hyperemesis, miscarriage
Can use carbimazole but not PTU (or radio-I2) to treat
Regular TFTs and multidisciplinary care
• If well controlled, no other impact on pregnancy
care (fetal growth, delivery etc)
• Inform Paeds to check fetal thyroid function,
especially if pt has thyroid Abs
Pre-Eclampsia
Definition
• Hypertension and proteinuria with onset ≥20 weeks
– Oedema from classical definition dropped as not
discriminating clinically
• Diastolic ≥90mmHg on 2 occasions 4-6 hours apart
OR ≥110mmHg on one occasion
• Proteinuria >300mg/24 hours
• Symptoms
• Differentiation from PIH/renal disease
PET/Eclampsia
George Eliot Hospital, Nuneaton
32
Hypertensive disorders
Raised BP in pregnancy
> or = 140/90
Pregnancy induced hypertension
(Raised BP after 20 weeks)
No proteinuria PIH
Mild and moderate PET
PET/Eclampsia
Chronic hypertension
(Raised BP before 20 weeks gestation)
Proteinuria and Raised BP
Pre -eclampsia
Severe PET
Eclampsia
George Eliot Hospital, Nuneaton
HELLP
33
Incidence
• 2-3% pregnancies
• 5-7% primips
• 1.8% PET will develop eclampsia (from
Collaborative Eclampsia Trial = 49/ 100000)
• Rates eclampsia 26.8/100 000 maternities
(UKOSS reporting system 2003-5)
• Worldwide 1.5-8 million develop PET with 150
000 deaths
• Deaths 2003-5: 0.85/100000 maternities
• 18 deaths
• 10 cerebral haemorrhage, 2 cerebral infartion
• 6 were eclamptic, 8 had HELLP syndrome
PET/Eclampsia
George Eliot Hospital, Nuneaton
34
Importance
• Maternal morbidity
– Blindness
– Neurological
– renal
• Fetal death
– Abruption, hypoxia, IUGR
• Fetal morbidity
– Prematurity (PET is cause of >40% iatrogenic preterm dels)
with risks respiratory and neurodevelopmental
complications (inc.learning difficulty/IQ in up to 60%)
PET/Eclampsia
George Eliot Hospital, Nuneaton
35
Risk Factors:-Pre-Eclampsia
• Primiparous
• First pregnancy with
new partner
• Family history (1 in 3
risk if mother had PET)
• Twins/multiples
• Pregestational Diabetes
PET/Eclampsia
•
•
•
•
Essential hypertension
Renal disease
SLE
Antiphospholipid
syndrome
• Thrombophilias
• Age >40
• Obesity
George Eliot Hospital, Nuneaton
36
Pathophysiology
• “The disease of theories”
• Pregnancy specific syndrome
• Placenta has a central role to play
– Reduced placental perfusion
– Inadequate vascular remodelling at ~16 wks
• Genetic component in some women tho’ not in
others
– No candidate genes or consistent results
PET/Eclampsia
George Eliot Hospital, Nuneaton
37
Pathophysiology of PET
PET/Eclampsia
George Eliot Hospital, Nuneaton
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2 stage process
• Inadequate implantation
• Poor remodelling
STAGE 1:Reduced
• Cytokines produced +
growth factors
• placental apoptosis/necrosis
• Shedding of microparticles into circulation
placental perfusion
• Markers seen
preceding PET
• Inflammation and
endotheial activation
PET/Eclampsia
STAGE 2: Maternal
syndrome
(multisystem
disorder)
George Eliot Hospital, Nuneaton
39
Prevention of PET: Aspirin
• Several small trials suggested reduction in rates PET
with low dose aspirin therapy
• Large multicentre trial (CLASP) in 9364 women did
not demonstrate benefit for wholescale prophylaxis
for low risk women
– Trend towards reduction in likelihood to preterm delivery
– No significant increased risk of haemorrhages
– No statistically significant effect on stillbirths/ neonatal
deaths
– Non significant (12%) reduction in incidence PET
Lancet 1994; 343: 619-629
PET/Eclampsia
George Eliot Hospital, Nuneaton
40
CLASP
• Trial suggested only
benefits in women at high
risk of severe early onset
IUGR ? How to identify
• Benefits thus suggested in
women with previous
severe early onset PET and
IUGR
• ?relationships to APLS (not
investigated in original trial)
PET/Eclampsia
George Eliot Hospital, Nuneaton
41
Prevention: Aspirin
• More recent study showed aspirin treatment
produced at RR of 0.9 (95% CI 0.84-0.97) for
PET
• Moderate but consistent reductions in PET,
preterm delivery and serious outcomes
Lancet 2007
PET/Eclampsia
George Eliot Hospital, Nuneaton
42
Prevention: Calcium
• Calcium levels lower in women with PET
compared to ‘normal’ pregnancy
• Australian Randomised Study in 456 singleton
nullips from <24/40 showed reduction in risk
PET with 1.8g calcium/day compared to
placebo
• RR 0.44 95% CI 0.21-0.90
Aus NZ J Obstet Gynaecol 1999; 39: 12-18.
PET/Eclampsia
George Eliot Hospital, Nuneaton
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Prevention: Calcium
• Calcium for Eclampsia Prevention Study (CPEP)
Am J Obstet Gynecol 1997; 177: 1003-10
• 4589 US women in multicentre trial
• All nullips
• Analysis of risk factors for development of
subsequent PET did not show any benefit
from Ca++ supplementation
PET/Eclampsia
George Eliot Hospital, Nuneaton
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Prevention: Calcium
•
•
•
•
Cochrane Review Cochrane Database 2000 (3), OUS.
9 studies, all good quality
Ca++ dose > 1g/day
Modest reduction in risk PET for all women (RR 0.72, 95% CI
0.6-0.86)
• Greatest effect where highest risk- RR 0.22, 0.11-0.43 and
low dietary intake (0.32, 0.21-0.49)
• No effect on preterm delivery
• Smaller effects seen for hypertension
– Ca++ appears of benefit for women at high risk of developing PET
– Also women from communities with low dietary intake
– Optimum dosage requires further evaluation
PET/Eclampsia
George Eliot Hospital, Nuneaton
45
Prevention: Antioxidants
• Vitamin C 1000mg and Vit E 400 IU/day
• 58% reduction in PET in treated group
Chappell et al, Lancet 1999 354: 810-5
• A number of trials ongoing globally
• All using above dosages
• 3 reported so far-NO difference in rates
treatment vs placebo.
PET/Eclampsia
George Eliot Hospital, Nuneaton
46
Diagnosis: Pre-Eclampsia
• Classic triad
– Hypertension 140/90
– Proteinuria >300mg in 24 hours (RCOG)
– Oedema (least reliable)
• BP rise should be from booking >30/15
• Proteinuria and raised BP x 2 occasions 6 hrs apart
(or once if DBP ≥110 and heavy proteinuria >2+
(=1g/24h))
PET/Eclampsia
George Eliot Hospital, Nuneaton
47
Mild PET
•
•
•
•
Classically asymptomatic
BP 140/90 (ish)
Maybe trace-+ proteinuria
Often incidental finding at CMW clinic
attendance
PET/Eclampsia
George Eliot Hospital, Nuneaton
48
What questions should you ask?
What questions should you ask?
• Headache (classically severe)
– Effects hypertension
• Visual disturbances (‘flashing lights’)
– Sign of cerebral vasospasm/impending eclampsia
• Epigastric pain
– Hepatic congestion/liver capsule stretching
• Is baby moving normally?
– Fetal wellbeing
What investigations should you
arrange?
• Maternal
• Fetal
PET-Investigations
•
•
•
•
•
•
FBCU+E
Urate
LFTs
Clotting
MSU
PET/Eclampsia
platelet count
signs renal dysfunction (late)
hyperuricaemia ( early )
elevated transaminases
XXXX (not routinely if plts>100)
to exclude UTI as cause of protein
George Eliot Hospital, Nuneaton
52
PET
• Fetal assessment
– Clinical
– USS for growth
– CTGs
• ?cervical assessment (depending on gestation)
PET/Eclampsia
George Eliot Hospital, Nuneaton
53
Monitoring
• Monitor BP
– CMW
– Day assessment or Triage Unit
• Monitor bloods
– Weekly or twice weekly (depends on sitn)
• Monitor fetus
– CTG
– Serial USS
PET/Eclampsia
George Eliot Hospital, Nuneaton
54
Definitive treatment
• Deliver when
– BP/protein or clinical condition deteriorates so
become moderate or severe PET
– Reaches 41 weeks and no change in condition
– Fetal condition mandates delivery even if
maternal condition stable
PET/Eclampsia
George Eliot Hospital, Nuneaton
55
Severe pre-eclampsia
• Hepatic
• SYSTOLIC 160-180
• DIASTOLIC >110
• CNS
– Abnormal LFTs, dysfunction
– RUQ pain
– Epigastric pain
– Headache
– Visual disturbances
– Disorientation/
irritability
– Hyperreflexia
– clonus
PET/Eclampsia
• Renal
– Elevated creatnine, urea,
urate
– Oliguria
– Heavy proteinuria >5g in 24
hrs
• Haemtological
– Thrombocytopaenia
– haemolysis
George Eliot Hospital, Nuneaton
56
Multisystem disease
• Eyes
–
–
–
–
–
• Liver
– Subcapsular haemorrhages
– Liver rupture
Arteriolar spasm
Retinal haemorrhages
Blindness
Scotoma
Papilloedema
• Kidneys
– Acute renal failure
• Fetoplacental Unit
• CNS
–
–
–
–
Seizures
Encephalopathy
Cerebral haemorrhages
CVA
• Respiratory
– Pulmonary oedema
– ARDS
PET/Eclampsia
–
–
–
–
IUGR
Abruption
Fetal compromise
Fetal death
• Haemotological
– DIC
– haemolysis
George Eliot Hospital, Nuneaton
57
Symptoms
•
•
•
•
Headache (BP)
Flashing lights (lightning) (cerebral oedema)
Epigastric pain (stretching of liver capsule)
Oedema (albumin/BP)
• Asymptomatic
PET/Eclampsia
George Eliot Hospital, Nuneaton
58
Management of severe pre-eclampsia
• Immediate admission to hospital
• High dependency care/LW-QUIET
– Invasive monitoring
– NICU for baby if early gestation
• Senior multidisciplinary involvement early-obs and
anaesthetics
PET/Eclampsia
George Eliot Hospital, Nuneaton
59
Aims of treatment
• Aims
– Prevent seizures
– Control hypertension (to prevent cerebral
haemorrhage)
– Deliver safely (stabilise, +/- IUT, +/- steroids)
PET/Eclampsia
George Eliot Hospital, Nuneaton
60
Maternal Assessment
•
•
•
•
•
BP-check every 15 minutes
Urine output-hourly
Urinary protein dipstix
Strict fluid balance chart
Bloods
– U+E, urea, creatnine, urate
– FBC esp. platelets (G+S)
– LFTs
• Deep tendon reflexes and presence of clonus
• CTG
PET/Eclampsia
George Eliot Hospital, Nuneaton
61
Control blood pressure
• Antihypertensives – aim for diastolic 85-95
– IV hydralazine (5mg every 15 minutes to acutely control
BP)
– IV labetolol (Not good if asthmatic or already signs of
pulmonary oedema-first line in many places now)
– Oral nifedipine 10mg NOT SUBLINGUAL
– Methyldopa TOO SLOW ONSET (24-48 hours) for use in
acute situation
– Titrate IV antihypertensive vs. BP then infusion
PET/Eclampsia
George Eliot Hospital, Nuneaton
62
KEY POINTS: Hypertension
Systolic blood pressure of 160 mm/Hg or more =
anti-hypertensive treatment.
(irrespective of diastolic)
Consideration starting treatment at lower pressures if the overall
clinical picture suggests likely rapid deterioration with
anticipation of severe hypertension.
PET/Eclampsia
George Eliot Hospital, Nuneaton
63
Prevent Fits
• Magnesium sulphate
–
–
–
–
–
–
–
–
PET/Eclampsia
All severe and moderate PET (MAGPIE)
4g IV over 15 minutes
Then infusion 1g/ hour
Monitor reflexes (present) urine OP (>30ml/hr) and
respiratory rate (>12/minute)
Slows neuromuscular conduction and decreases CNS
irritability
Best anticonvulsant in these circumstances AND IN
ECLAMPSIA
No effect on BP
Tell anaesthetist if GA as potentiates effects of muscle
relaxants
George Eliot Hospital, Nuneaton
64
Magnesium toxicity
• If urine OP OK then likely • Magnesium levels
– Therapeutic 2-4 mmol/l
not to accumulate (85%
– Warmth, flushing, slurred speech
renal excretion)
3.8-5mmol/l
• If urine output falls,
– Loss of patellar reflexes >5 mmol/l
reduce dose to 0.5g/hour
– Respiratory depression >6 mmol/l
• If signs toxicity, stop
– Respiratory arrest 6.3-7mmol/l
• Antidote = Calcium
– Cardiac arrest, asystole >12
gluconate 1g IV over 3
mmol/l
minutes
PET/Eclampsia
George Eliot Hospital, Nuneaton
65
MAGPIE
• 10141 women-99% received allocated treatment
• 24% of women with MgSO4 reported side-effects
compared to 5% of women on placebo
• MgSO4 produced 58% reduced risk of eclampsia
(0.8% cf. 1.9%)-across all categories of PET
• Maternal mortality lower as well RR 0.55, CI 0.26-1.14
• Only improvement in maternofetal morbidity was
reduced risk of abruption (0.67, 99% CI 0.45-0.89)
• No substantial harmful risks to mother or fetus
Lancet 2002; 359: 1877-90.
PET/Eclampsia
George Eliot Hospital, Nuneaton
66
MAGPIE
PET/Eclampsia
Lancet 2002; 359: 1877-90.
George Eliot Hospital, Nuneaton
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Deliver Baby
• If severe PET, should NOT transfer
• Ensure SCBU aware if baby premature
• Give antenatal steroids if time but usually, if require
IV therapy, delivery is indicated once stabilised
• If cervix favourable and patient >36 weeks, consider
short trial IOL
• If cervix unfavourable and/or <36 weeks, deliver by
LSCS
• Anaesthesia epidural vs. general
PET/Eclampsia
George Eliot Hospital, Nuneaton
68
DELIVERY: Key Points 1
Risk of sharp rise of BP on intubation
This may be obtunded by large dose
alfentanyl or similar
Need experienced and senior anaesthetist to
give GA in these circumstances
PET/Eclampsia
George Eliot Hospital, Nuneaton
69
DELIVERY: Key Points 2
Syntometrine should not be given for the
active management of the third stage if the
mother is hypertensive, or if her blood
pressure has not been checked.
(ergometrine causes vasospasm and a sharp rise in
BP which may precipitate hypertensive crisis, fits
or cerebral haemorrhage)
PET/Eclampsia
George Eliot Hospital, Nuneaton
70
Eclampsia
• Occurrence of fits
– 44% postpartum
– 38% antenatal)
– ALWAYS GRAND MAL
•
•
•
•
•
•
Due usually to cerebral vasospasm
Do not try to shorten initial convulsion (self-limiting)
Prevent maternal injury
Maintain oxygenation
Prevent aspiration
ABC…
PET/Eclampsia
George Eliot Hospital, Nuneaton
71
Eclampsia
• Beware known epileptics
– If BP normal, no protein, typical for their type
of fit-may be epilepsy BUT any fit must be
considered as eclampsia until proven
otherwise especially of BP slightly up etc
• Any FOCAL fit is not eclampsia
– Consider SOL eg cerebral bleed/infarction due
to severe PET
– Arrange head CT urgently
PET/Eclampsia
George Eliot Hospital, Nuneaton
72
Collaborative Eclampsia Trial
• Multicentre international trial
Lancet 1995; 345: 1455-63
• 1687 women
• Comparisons:
– MgSO4 vs. diazepam
• 52% lower risk recurrent convulsions with MgSO4
– MgSO4 vs. phenytoin
• 67% lower risk recurrent convulsions with MgSO4
• Maternal mortality nonsignificantly lower in MgSO4
• Less risk of pneumonia, ventilation, ITU with Magnesium
• Babies less likely to be intubated and go to SCBU
PET/Eclampsia
George Eliot Hospital, Nuneaton
73
Eclampsia
• Treatment is IV magnesium sulphate-4g loading then
1g/hr
• If recurrent fits or fit already on MgSO4, then further
2g IV bolus/increase infusion to 1.5g/hr
• If fits persist, check magnesium levels, contact
anaesthetists, consider CT, consider intubation and
ventilation
• If antenatal, stabilise and Deliver
PET/Eclampsia
George Eliot Hospital, Nuneaton
74
Postnatal care
• Watch closely on HDU/LW until diuresis and
condition improving
• Anticipate possible worsening or seizures in first 1824 hours
• Continue MgSO4 for 24 hours and then review
• Do not need to taper off MgSO4
• Do not feed within 12 hours as significant risk ileussips H2O only until next morning then review for
bowel sounds
PET/Eclampsia
George Eliot Hospital, Nuneaton
75
Postnatal Management-Hypertension
• Hypertension may persist for some weeks
• Switch to oral treatment when feasible
– Atenolol
– Nifedipine
• Polypharmacy may be required to control BPconsult with physicians
• Ensure regular BP checks arranged on
discharge with review and follow-up by GP
PET/Eclampsia
George Eliot Hospital, Nuneaton
76
Postnatal Management-Fits
• Eclampsia Survey showed 44% of fits occur
postpartum
• High index of suspicion
• Beware worsening of condition
• MgSO4 prophylaxis in all severe PET and all
eclamptics
• All women with severe PET should have
MgSO4 for 24 hours following delivery or
following last fit-whichever is longer
PET/Eclampsia
George Eliot Hospital, Nuneaton
77
Postnatal Management-Fluids
• Fluid overload real danger after delivery
– Relaxed vigilance
– LSCS
– PPH
– Physiological oliguria
• STRICT FLUID BALANCE
PET/Eclampsia
George Eliot Hospital, Nuneaton
78
Postnatal Management-Fluids
• SHIP audit (1997) showed that many women have
oliguria but intervention not required unless UO
<100ml in 4 hours
• Fluid overload carries risks of pulmonary oedema– Reduced plasma oncotic pressure
– Hypertension thus increased gradient across
microvasculature
– Filtration of fluid into tissues
– Pulmonary oedema
PET/Eclampsia
George Eliot Hospital, Nuneaton
79
Postnatal Management-Fluids
• Women with PET are very vulnerable to
Pulmonary oedema
• Carries risk of ARDS if severe or not
recognised rapidly
• ARDS may be fatal
• Fluid restriction is far SAFER
– Renal function more likely to recover than
pulmonary and less likely to kill pt
PET/Eclampsia
George Eliot Hospital, Nuneaton
80
Causes of death
SHIP
PET/Eclampsia
George Eliot Hospital, Nuneaton
81
Fluid Balance
• Take Home messages
– Fluid restrict as pt already fluid overloaded
– Scrupulous input and output
– Do not fluid challenge
– Do not give frusemide
– Consider CVP line if urine output poor
– Seek senior advice early
– Multidisciplinary Mx-obs/anaesth/renal teams
PET/Eclampsia
George Eliot Hospital, Nuneaton
82
GI management
• Don’t forget stress response to illness• H2 antagonists (eg Ranitidine)
• Delay feeding until bowel sounds present
– May develop ileus if v unwell
PET/Eclampsia
George Eliot Hospital, Nuneaton
83
Disease Progression
• Often improve quickly
• Some may deteriorate further immediately after
delivery –may continue to worsen for 24 + hours
–
–
–
–
Worsening BP
Worsening bloods
Oliguria/anuria
Increased risk fits
• Consult seniors and manage with
multidisciplinary team
PET/Eclampsia
George Eliot Hospital, Nuneaton
84
HELLP syndrome
•
•
•
•
•
Haemolysis
Elevated
Liver Enzymes
Low
Platelets
• 1-12% PET (usually severe
end of spectrum)
• Commoner in multips
• Variable presentation
– RUQ pain, epigastric pain,
nausea + vomiting
– 85% hypertensive at
presentation
• Present: 2/3 antepartum,
1/3 postpartum
– mid 2nd trimester to several
days postnatal
PET/Eclampsia
George Eliot Hospital, Nuneaton
85
Differential diagnosis in HELLP
• Any liver problems
– Biliary colic
– Cholecystitis
– Hepatitis
• Gatroenteritis or reflux
• Pancreatitis
• ITP/ TTP
PET/Eclampsia
• Ureteric colic
• Renal calculus
• Rare-if severe pain:
• Aortic dissection
• MI
George Eliot Hospital, Nuneaton
86
Management of HELLP
•
•
•
•
•
•
•
Treat as severe PET
Stabilise
Fluids
Antihypertensives
MgSO4
Anti-thrombotic agents
Coagulation factors (if
required)
PET/Eclampsia
• Assess baby
– USS
– CTG
• (remember 20% risk of
abruption)
• PLAN DELIVERY ASAP
• TRANSFER TO TERTIARY
CENTRE IF REQUIRED
• IOL or LSCS
George Eliot Hospital, Nuneaton
87
Summary-PET, eclampsia, HELLP
• Serious disease with potential for maternal
and fetal mortality
• Prevention not widespread ? Aspirin for some
? Calcium for all
• Treatment depends on prevention of
complications and timing delivery
• Senior involvement in severe cases
PET/Eclampsia
George Eliot Hospital, Nuneaton
88
Essential Hypertension
• Pre-existing raised blood pressure
• May be on treatment or just under
observation
• May be known prior to pregnancy or detected
at booking as raised BP
Cardiovascular changes of Pregnancy
• Massive changes in
cardiac output and
haemodynamics
• Already occurred
largely by 12 weeks
Haemodynamic changes of pregnancy
• Progressive rise
in HR
• Increase in SV by
10 weeks
• rise in CO
(CO=HR x SV)
• BP falls from end
first trimester
(fall in TPR)
• BP rises in late
pregnancy
Haemodynamic changes of pregnancy
• Cardiac output
– Increases by 40% (5l/min prepregnancy to 7l/min by 20 weeks)
– Mainly due to increased SV (10-20 ml)
• Maternal HR increases to 80-90bpm (15% ↑)
– ‘palpitations’
• TPR falls due to vasodilation
– Feeling hot
• BP falls during pregnancy but rises towards term
– fainting
Supine hypotension
•
•
•
•
•
•
•
Affects 10-15% of women
Aortocaval compression by gravid uterus
(usually from 20-24 weeks)
Reduces venous return  reduces CO
At term IVC may be totally occluded by uterus when supine
CO may reduce by 25-33%
Use of left lateral position or wedge/ tilt
– Pregnant women feel uncomfortable and may refuse to lie flat
– BP inaccurate in supine pregnant woman
Blood pressure changes
• Early pregnancy
– Reduced DBP but little change SBP wider pulse
pressure
– Traditionally use 4th Korotkoff sound for BP but
poorly reproducible-5th sound still more accurate
in pregnancy
• Changes reverse in 2nd half of pregnancy
Risks to Mum
• Worsening of BP
• Superimposed preeclampsia
• Medical overintervention
Risks to Baby
• Teratogenesis from
certain drugs (eg ACEI)
• IUGR
• Pre-eclampsia
• Hypoglycaemia if on
labetolol and
breastfeeding
Pre-pregnancy
• If planned, review medications
– Take off tertaogenic meds eg ACEI or similar
– Take off diuetics
• Optimise diet
• Stop smoking
• Start folic acid
Early pregnancy
•
•
•
•
•
•
Review meds at booking
Take off any teratogenic meds
Start folic acid
Early booking at hospital for risk review
Dating scan +/- NT (combined) scan
Plan for pregnancy
– Including issues re: obesity, screening for GDM
Pregnancy
• Regular BP checks
• May need to come off
meds if BP ↓↓
• May need to start or
restart meds later in
pregnancy as BP rises
• ? Growth scans
• Joint care between MW
and hospital
Later Pregnancy
• If BP well controlled and fetal growth normal,
aim to labour spontaneously or induce as
postdates
• If BP raised, try control first with medications
• If superimposed PET or fetal growth issues,
consider delivering early
• NO ERGOMETRINE at delivery-syntocinon only
Post delivery
• Watch BP for at least 24-48 hours
• May need oral antihypertensives
• Communicate closely with GP to ensure that
BP monitoring is taken over and ongoing care
is handed over to GP
Cardiac Disease
• Pre-existing/congenital
– Valvular disease
– coarctation
• Acquired
– IHD
– Aortic aneurysm
– cardiomyopathy
Importance
• Leading Indirect Cause
• Rate 2.27 / 100 000
of Maternal Death AND
maternities -rising:
the most common
• 2002-2 2.20
single cause of maternal • 1997-9 1.65
death!
• 48 women 2003-5
• 46% had substandard
care
Prepregnancy
• Review by cardiologist
– Including advice whether should risk pregnancy
•
•
•
•
Optimise condition
Advice regarding pregnancy
Stop smoking
Start folic acid
New York Heart Association Heart
Functional Classification.
Class I
Patients have no limitation of physical activity. Ordinary physical activity does
not cause undue fatigue, palpitations, dyspnoea or anginal pain.
Class II
Patients have slight limitation of physical activity. Ordinary physical activity
results in fatigue, palpitations, dyspnoea or anginal pain.
Class III
Patients have marked limitation of physical activity. Less than ordinary activity
causes fatigue, palpitations, dyspnoea or anginal pain.
Class IV
Patients have inability to carry out any physical activity without discomfort.
Symptoms of cardiac insufficiency or of anginal syndrome may be present,
even at rest. If any physical activity is undertaken, discomfort is increased.
Risk of Mortality <1%
•
•
•
•
•
•
•
ASD
VSD
PDA
Pulmonary/tricuspid disease
Corrected Tetraology of Fallot
Mitral stenosis, Functional Classes 1 and 2
Prosthetic valve (animal)
Risk of Mortality 5-15%
•
•
•
•
•
•
•
•
Mitral stenosis with AF
Artificial Valve
Mitral stenosis (Class 3 and 4)
Aortic stenosis
Coarctation of the aorta
Uncorrected tetralogy of Fallot
Previous MI
Marfan’s Syndrome with normal aorta
Risk of Mortality 25-50%
• Pulmonary hypertension (Primary and
Eisenmengers)**
• Coarctation of the Aorta, complicated
• Marfan’s Syndrome with Aortic Involvement
• Previous cardiomyopathy, residual ventricular
dysfunction**
• **would usually counsel against ever
conceiving
At Booking.
• All women should have their health assessed and history of
previous murmur, cardiac disease or risk factors for coronary
artery disease (obesity, smoking, diabetes, hyperlipidaemia, preexisting hypertension, age >35, positive family history for ischaemic
heart disease)
– should be counselled to inform attendants should they develop any
symptoms of chest/arm/jaw pain, shortness of breath, palpitations.
• All immigrant women should undergo cardiovascular examination
at booking by an appropriately trained professional (GP,
obstetrician)6.
• Women with known cardiac history should have early referral and
details of their condition should be sought urgently from GP or
cardiologist.
– They should be urgently assessed by consultant obstetrician and/or
cardiologist. Referral to tertiary centre (specific antenatal cardiology
clinic at BWH) may be necessary.
In Pregnancy
• Should patient stay in your unit?
– High risk cases should be transferred to unit with
specialist antenatal cardiology service (eg BWH)
• Is there a risk of cardiac defect in fetus?
– Congenital cardiac disease eg Fallot, coarctation,
ASD/VSD, valvular disease ALL carry increased risk
of cardiac disease in fetus (2-5%) thus qualify for
detailed fetal echocardiogram in BWH Fetal
Medicine Centre
In Pregnancy
• Should you continue with the pregnancy?
– Pulmonary hypertension carries 50% risk of death.
Patients should be aware of the very real risks of
dying and be given the choice
• Is there anything special I need to do for
pregnancy?
– In terms of monitoring, medication, scans etc
– Eg antibiotics to cover labour, no ergometrine at
delivery
In Pregnancy
• Mode of delivery?
– Caesarean or vaginal?
– Allow pushing or shorten second stage?
– Epidural to reduce rise in heart rate
• Anaesthetic issues?
• Care and monitoring following delivery?
• Advice re: contraception following delivery
Common Problems in Pregnancy
• Palpitations
• Common.
• Many are merely ectopic beats but a few may be
genuine SVTs.
– Check Hb, Thyroid function and perform basic
cardiovascular examination (pulse, BP, JVP, auscultation
chest and heart, look for oedema). Pulse >100 should
prompt immediate ECG and medical review.
– Arrange ECG as outpatient if pulse less than 100 and
regular.
– Organise review with Physician
– Further investigations may include 24 hour ECG tape but
many women will be reassured and discharged back to
normal care.
Common Problems in Pregnancy
• Supraventricular Tachycardias (SVT)
• Not uncommon as known pre-existing condition
• Investigate as palpitation but more urgently(if
occur de novo)!
• Drugs used to treat known cases (eg verapamil,
flecainide) do not affect fetus and are not
associated with teratogenic effects and patient
should be reassured of this.
• Ensure regular review with their cardiologist but
treat pregnancy otherwise as normal.
Common Problems in Pregnancy
Heart Murmurs.
Commonly heard in pregnancy. Many are flow murmurs but some may
represent valvular disease or septal defects.
•
•
•
•
•
Investigations:
Arrange Physician or Cardiologist
review
Check function status-any symptoms?
Arrange ECHOCARDIOGRAM
If valvular lesion seen (NOT mitral
valve prolapse) ensure fetus has
cardiac scan arrange at detailed USS .
•
•
•
Management.
1. If flow murmur only  reassure
patient. No further action required.
2. If valvular lesion (stenosis,
incompetence or MVP) (see below for
more details) give antibiotics to cover
labour.
– Refer cardiologist for assessment.
– Arrange cardiac scan for fetus
•
3. If septal defect (VSD, ASD), arrange
cardiology review.
– Antibiotics to cover labour or invasive
procedures
– Fetal cardiac scan
Suspected Cardiac Disease In
Pregnancy
• Clinicians should have a low threshold for investigating
women (especially those with the risk factors for cardiac
disease) who complain of
– severe chest pain,
– chest pain that radiates to the neck, jaw or back,
– chest pain associated with other features such as agitation,
vomiting or breathlessness, tachycardia, tachypnoea or
orthopnea.
• Remember that shortness of breath, wheezing, palpitations
and irregular heart beat may all be symptoms of/associated
with heart failure. All women with these symptoms should
be undergo and proper full cardiovascular and respiratory
examination. If in doubt, seek senior advice.
Suspected Cardiac Disease In
Pregnancy
• Management:
– 15 minute observations and MEWS chart should be started with
continuous electronic fetal monitoring if the pregnancy is 25
weeks or above.
– The patient should be managed as a potential high dependency
case.
– Observations should include respiratory rate and oxygen
saturations as well as temperature, pulse and blood pressure.
• Appropriate investigations include chest X-ray (CXR), ECG,
cardiac enzymes (Troponin T), Echocardiogram and CT
pulmonary angiography.
– NB: if the clinician is not confident or competent to interpret the
ECG, he should show it to someone who is.
Suspected Cardiac Disease In
Pregnancy
• The Medical Registrar, though familiar with
management in non-pregnant patients, may
not be so familiar with disease in pregnancy
• He might benefit from input from obstetric
team in jointly managing the case.
• Teams are told to contact obs consultant and
potentially the medical consultant if still
unhappy with the advice given.
If a patient is very short of breath
and obviously pregnant, what is
the first diagnosis you will think of?
Venous Thromboembolism
• Leading direct cause of maternal death
• Second most common cause overall
– 1997-9
– 2000-2
– 2003-5
35 deaths
30
41
– Rate 1.43/100 000 maternities
– in pregnancy risk VTE 60/1000
• cf 1/1000 nonpregnant, no hormone,
• 15/1000 3rd gen COCP,
• 30/1000 2nd gen COCP
Risk Factors for VTE
• Known thrombophilias e.g. Protein S or Protein C deficiency, Factor
V Leiden, Anti-Thrombin III deficiency
• Antiphospholipid syndrome
• Previous DVT or PE
• Strong family history VTE (DVT/PE)
• Obesity (BMI ≥30)
• Age >35
• Pre-eclampsia
• Parity >3
• Paraplegia
• Sickle cell disease
• Inflammatory disorders and infection e.g. inflammatory bowel
disease and UTI
Risk Factors for venous thromboembolism in pregnancy or
the puerperium
PRE-EXISTING
– Previous VTE
– Thrombophilia
• Congenital
• Acquired
–
–
–
–
–
–
–
–
Obesity BMI>30
Para>4
Gross varicose veins
Paraplegia
Sickle cell disease
Inflammatory disorders
Some medical disorders
Myeloproliferative disorders
NEW ONSET OR TRANSIENT
– Surgical procedure in pregnancy or
puerperium
– Hyperemesis
– Dehydration
– Severe infection eg pyelonephritis
– Immobility >4 days bedrest
– Pre-eclampsia
– Excessive blood loss
– Long haul travel
– Prolonged labour
– Midcavity instrumental delivery
– Immobility after delivery
Review of underlying physiology
• Pregnancy is pro-thrombotic
• Compounded by effects of Virchow’s triad
– Stasis
• Secondary to venous compression by pregnant uterus
– Hypercoagulability
• Effects of pregnancy
– Vascular damage
• Varicose veins
Coagulation changes in pregnancy
• Increased levels
factors VII, VIII, X
and Fibrinogen
• Effects on both
intrinsic and
extrinsic
pathways
Reducing the Risk in Pregnancy
• Score all women at booking (on basis weight/history etc)
• If possible increased risk on basis of personal or family history but does
not fulfil criteria for immediate prophylaxis, discuss with consultant.
• One option is to investigate if persuasive reasons to do so (eg unexplained
poor obstetric history, no family history available as adopted etc)
– perform FBC, clotting studies, thrombophilias screen, anti-cardiolipin, lupus
anticoagulant screening.
– Be aware levels of Proteins S and C alter during pregnancy.
• Even if patient does not require prophylaxis usually, reconsider if:
– Dehydration e.g. hyperemesis, OHSS, prolonged vomiting+pyrexia
– Immobility e.g. bedrest for symphysis dysfunction, illness including
dehydration, paraplegia
– Any surgery considered even if not gynaecological
Which agent, how to start prophylaxis
and how much?
• Low molecular weight heparin is the default
agent
– George Eliot Hospital currently uses Enoxaparine
• Dose dependent on booking weight
– Warfarin is associated with 6% risk warfarin
embryopathy so should only be used where heparin is
considered unsuitable such as in some women with
mechanical heart valves
– Oral thrombin and Xa inhibitors (Dabigatran and
rivaroxaban) are not licensed for pregnancy and there
is no experience of their use. Therefore they should be
avoided in pregnant women.
Risk
Who should have antenatal
prophylaxis?
History
Prophylaxis
Very high



Previous VTE on long-term warfarin
Antithrombin deficiency
Antiphospholipid syndrome with previous
VTE
Recommend antenatal high-dose LMWH and at least
6 weeks postnatal LMWH/warfarin
Requires specialist management by experts in
haemostasis and pregnancy
High


Previous recurrent or unprovoked VTE
Previous
estrogen-provoked
(pill
or
pregnancy) VTE
Previous VTE + thrombophilia
Previous VTE + family history of VTE
Asymptomatic
thrombophilia
(combined
defects, homozygous FVL)
Recommend antenatal and 6 weeks
postnatal prophylactic LMWH
Single previous VTE associated with
transient risk factor no longer present without
thrombophilia, family history or other risk
factors
Asymptomatic
thrombophilia
(except
antithrombin deficiency, combined defects,
homozygous FVL)
Consider antenatal LMWH (but not routinely
recommended)
Recommend 6 weeks postnatal prophylactic LMWH
Recommend 7 days (or 6 weeks if family history or
other risk factors) postnatal prophylactic LMWH



Intermediate


FVL = factor V ; LMWH = low-molecular-weight heparin
What symptoms are you looking for in
possible VTE?
What symptoms are you looking for in
possible VTE?
•
•
•
•
Shortness of breath
Pleuritic chest pain
Haemoptysis
Collapse
• Symptoms of DVT– leg pains or discomfort, swelling and tenderness,
oedema
– More common on left
– Usually iliofemoral in pregnancy
Investigations-DVT
Investigations-DVT
• FBC, baseline coagulation screen, U&E, LFT
• D dimer (negative predictive value still useful
but almost ALL women test positive anyway in
late pregnancy)
• Thrombophilia screen not indicated at this
stage
Imaging in DVT
• Compression duplex USS test of choice
– If negative and low level clinical suspicion-discontinue Rx
– If still high level clinical suspicion-continue LMWH and repeat USS
in 1 week
– Or try alternative modality
• If suspect iliac DVT, consider MR venography or
conventional venography
Doppler ultrasound
Investigations - PE
Investigations - PE
• Blood tests as above
• ECG
• Chest X-Ray
PE
• CXR should be performed in all women
– Normal >50% women with objectively proven PE
– But PE may cause atelectasis, effusion, focal
opacities, regional oligaemia or pulmonary
oedema
• If negative, bilateral compression Duplex
dopplers should be performed
• Radiation dose to fetus is negligible at all
gestations
PE: next steps
• CTPA if still clinical suspicion in non-massive
PE
– Lower radiation dose to fetus
– Better sensitivity and specificity in non-pregnant
women (BTS)
– Can detect other pathology e.g. aortic dissection
CTPA: radiation issues
• Higher radiation dose to maternal breasts
– (20 mGy)-dose of >10 mGy increases lifetime risk of Ca breast
• Increased risk estimated at 13.6% (background 1/200)
– Prob overestimate in non-pregnant woman
– BUT breast in pregnancy more sensitive?
• Women with +ve/strong FHx?
CTPA: radiation issues (2)
• 10% dose to fetus of V/Q scan
• Risk of childhood cancer 1/1 000 000 after
CTPA vs 1/280 000 with V/Q
V/Q?
• Traditionally investigation of choice
• BUT geographically limited (travel to another
unit)
• Limited availability due to isotope availability
(waiting for availability-bed occupancy,
unnecessary anticoagulation, separation from
family)
• Also radiation issues
V/Q
•
•
•
•
Less sensitivity and specificity
Equivocal results?
High negative predictive value
BUT Ventilation scan may be preferable in
women with FHx Ca breast
Pulmonary angiography
• Highest radiation dose to fetus (0.5 mSv) and
to maternal breast (5-30 mSv)
Massive life-threatening PE
• Medical emergency
• Full medical team + consultant obstetrician +
senior radiologist
• Urgent portable ECHO +/- CTPA within 1 hour
of admission
• May decide therapy before confirmation
(thrombolytic Rx/IV heparin/embolectomy
etc)
Suspected VTE in pregnancy
•
“Treat then see”
• Immediately start therapeutic LMWH
• (1mg/kg prepregnancy wt/12hrs)
• Then arrange diagnostic tests
Treatment
• LMWH from suspicion
• Treatment dose-1mg/kg bd
• Continue until delivered (+6 weeks) or 6
months postnatal, whichever is longer
Antiphospholipid Syndrome (APLS)
• Presence of antiphospholipid antibodies(aPL)antiCardiolipin (aCL) and lupus anticoagulant
(LA) with one or more of the characteristic
clinical features = APLS
Criterion
Description
Thrombosis
Venous
Arterial
Small Vessel
Pregnancy Morbidity
3 consecutive miscarriages <10 weeks
1 fetal death (>10 weeks gestation with fetal
heart documented)
1 premature birth (<34 weeks gestation) due to
pre-eclampsia or placental insufficiency
APLS
• First described in patients with SLE but now we
know
• Most APLS do not fulfil criteria for SLE
• Those with primary ALSP do not progress to SLE usually
• Though clinical features Primary and SLE-associated APLS are
similar, the distinction is important and primary APLS should
not be labelled as SLE
•
•
•
•
aPL in general obstetric population is <2%
About 30% SLE have aPL
About 30% aPL have thrombosis
Up to 30% early onset PET have aPL
Diagnosis
• Two or more positive reading for LA and/or
aCL at least eight weeks apart as well as one
of features in table
Effects of Pregnancy on APLS
• Thrombosis risk worsens due to
hypercoagulable state of pregnancy
• Pre-existing thrombocytopaenia may worsen
Effects APLS on Pregnancy
•
•
•
•
•
•
First trimester Miscarriage
Second trimester fetal loss
Third trimester fetal death
PET
IUGR
Abruption
Management
• Prepregnancy
– Screen for aPL if suspicious history
– Detailed history of loss to ascertain cause
• Antenatal
–
–
–
–
–
–
–
–
–
Early booking
Viability scanning
Low dose aspirin 75mg od and LMWH
Switch from warfarin to LMWH by 6 weeks
Detailed USS with uterine artery dopplers
Serial growth scans
Monitor for PET
Fetal wellbeing assessment
Elective delivery at 37-38 weeks
Postnatal Management
• Women on long term warfarin may restart on
day 2-3 and stop LMWH when INR is 2.0
• All women should have postpartum LMWH for
six weeks
Thrombophilias
•
•
•
•
•
•
Antithrombin III deficiency
Activated Protein C resistence
Protein C deficiency
Protein S deficiency
Prothrombin gene mutation
Factor V Leiden
• May be known or only suspected due to effects
Thrombophilias
• Risks
–
–
–
–
–
–
VTE
Recurrent miscarriage
Second trimester Pregnancy Loss
IUGR
Pre-Eclampsia
Stillbirth
• All less common than in APLS but can still be
serious in any individual woman
Thrombophilias
• Pre-pregnancy
– Review history
– Change off any medications eg warfarin that are
contraindicated in pregnancy
– Stop smoking, start folic acid
• Early Pregnancy
– Aspirin from +ve UPT
– Early viability scan 6-8 weeks
– Start LMWH OD from +ve fetal heart
Thrombophilias
• Pregnancy
– Regular antenatal care
– Anomaly USS +/- uterine artery dopplers
– Serial growth scans
– Consider early delivery eg 38-40 weeks
– Plan stopping aspirin/LMWH prior to labour
• Postnatal
– LMWH for 6 weeks minimum VTE prophylaxis
ASTHMA
• Commonest chronic medical illness to
complicate pregnancy
• Up to 7% women of childbearing age
• Often undiagnosed or undertreated
Respiratory Changes in Pregnancy
• Increased resp rate– Causes resp alkalosis
•  pH 7.43 (pH 7.40 non-pregnant)
•  pCO2 4.3 kPa (5.3 kPa)
•  HCO3- 20.0mmol (24.2 mmol)
• Changes in PFTs due to mechanical effects of
pregnancy on lungs…
Respiratory Changes in Pregnancy
• ↑O2 demand-20%
•
increased consumption
•
• Tidal volume increases
•
• (and with small ↑ in
respiratory rate= large
increase on ventilation-4050% ↑in minute
ventilation)
•
• Inspiratory capacity
increases
Residual volume decreases
Expiratory reserve decreases
Marked reduction in functional
residual capacity
– Diaphragmatic elevation
– Increase in subcostal angle and
transverse thoracic diameter
FEV1 and PEFR are
unchanged
Respiratory Changes
• Increased tidal volume –marked increase in
ventilation
– Enhanced gas transfer (also helped by improved
pulmonary blood flow)
– pCO2 is reduced by 15-20% while pO2 is only
marginally altered
– This is offset by increase in 2,3 DPG in maternal
RBC shifts dissociation curve to RIGHT so that
maternal O2 saturation changes little
– This enhances O2 transfer to fetal RBC which
have dissociation curve shifted to LEFT
• Fetal Hb much higher affinity for oxygen than
adult Hb
• Fetal Hb much less sensitive to 2,3 DPG
Respiratory Changes
• Progesterone effect probably underlies changes in
ventilation and reduction in CO2
• Directly on respiratory centre
• Increases carbonic anhydrase in maternal RBC
– Increased breakdown of CO2 and excretion of HCO3 through maternal
kidneys
• Functional changes though facilitate airflow along bronchial
tree
• Women with chronic respiratory disease tend to deteriorate less
in pregnancy
• Peak expiratory flow and FEV1 can still be valid in pregnant
asthmatics
• Shortness of breath is common symptom in pregnancy
• Individual variations in chemoreceptors
• Physiological increase in proportion of blood shunted away from
functioning alveoli
Effects of Pregnancy on Asthma
• May improve, deteriorate or remain unchanged
• Mild disease-unlikely to experience problems
• Severe disease-greater risk of deterioration, esp
in 3rd trimester
• Improvement in 3rd trimester may experience
postnatal deterioration
• Deterioration often due to reduction or cessation
of medications due to (unfounded) safety fears
Effects of Asthma on Pregnancy
• Most women-no adverse effects on pregnancy
outcome
• Severe, poorly controlled-asthmatics associated with
hypoxaemia may adversely affect fetus
• Adverse effects on pregnancy rare and associated with
poor control
–
–
–
–
–
PIH/PET
PTL/birth
LBW
IUGR
Neonatal morbidity eg TTN, hypoglycaemia, seizures, NNU
admission
Management
• Emphasis on prevention rather than
treatment
• Treatment in pregnancy is no different to nonpregnant women
– Optimise control prior to pregnancy
– Achieve control asap in new diagnosis
– Use of B2 agonist +/- inhaled corticosteroids
mainstay
Medication Issues
• B2 agonists
– Safe in pregnancy
– Serevent experience growing and ALSO appears
safe
• No adverse fetal effects reported with the use
of the following inhaled drugs
– Disodium chromoglycate
– Nedocromil
– Anticholinergics
Medication Issues
• Steroids
– Inhaled:
• minimal absorption
• No evidence fetal malformations or adverse fetal effects
– Oral
• Should not be withheld in acute attacks
• No strong evidence of fetal malformations, miscarriage,
stillbirth or neonatal death
• Will worsen glycaemic control in diabetics or may increase
risks GDM with long-term use
• Long-term high dose steroids ↑risk premature ROM
Acute Asthma Attack
• Manage as non-pregnant
–
–
–
–
IV rehydration
O2
B2 agonists as O2 nebuliser (may be repeated)
CXR if suspicion pneuthorax/pneumonia or failure to
improve
– If PEFR fails to improve to >70% predicted, ADMIT
– Give steroids JUST AS IF pt was not pregnant! (often
inappropriately withheld)
– If not improving, may need IV steroids, IV
aminophylline or IV B2 agonists
Pregnancy Care
• Regular antenatal care in conjunction with
professional in charge of asthma care
• Growth scans only in poorly-controlled
disease-if well-controlled, treat as normal
• GTT if on oral steroids
• Induce only for good obstetric reasons
– Induction (PGE2) drugs are NOT contraindicated
(they actually act as bronchodilators)
Intrapartum Management
• No contraindication to induction
• If oral steroids for >2 weeks prior to labour, will need IV
hydrocortisone
• Prostaglandin F2a can cause bronchospasm so should
be used with caution (but not withheld if lifethreatening haemorrhage)
• All forms of pain relief may be used
• Ergometrine associated with bronchospasm-avoid
• Encourage breastfeeding to reduce risk of atopic
disease in child (1 in 10 or 1 in 3 if both parents atopic)
– All drugs discussed above safe in breastfeeding
EPILEPSY
• About 0.5% women of
childbearing age
• Most diagnosed (known)
prior to pregnancy
• All seizure types may be
affected by pregnancy
• Associated with risks
maternal death due to
aspiration and SUDEP
Effect of Pregnancy on Epilepsy
• 25-30% ↑seizure frequency
• 54% no change
• If seizure free unlikely to have seizures UNLESS
stops medications
• Poorly-controlled (>1/month) likely to
deteriorate in pregnancy
• Risk of seizures highest in peripartum period
Reasons for Deterioration of Control
• Pregnancy
• Poor compliance (Fears of teratogenesis)
• Decreased drug levels due to nausea and
vomiting
• Decreased drug levels due to ↑volume of
distribution and ↑drug clearance
• Lack of sleep towards term and during labour
• Lack of absorption of drugs during labour
• Hyperventilation during labour
Effects of Epilepsy on Pregnancy
• Fetus is relatively resistant to short-term hypoxia
(during seizures)
• No evidence adverse effects
• No increased risks of miscarriage or obstetric
complications (IUGR, PTL, PET etc)
• Status Epilepticus <1% pregnancies BUT dangerous for
mum and baby-TREAT VIGOROUSLY!
• Major risk is teratogenicity of drugs
• Even women on no Rx have ↑risk malformations (4% vs 3% in
general population)
• Risk of chid developing epilepsy
•
•
•
•
5% if either parent has epilepsy
15-20% if both
10% if affected sibling and <2 parents affected
9-12% if parent has idiopathic generalised-only 3% if partial
seizures
Teratogenic Risks of Anticonvulsants
• ALL are teratogenic-newer drugs thought to be
safe but now shown to have risks associated with
use
• Major malformations are:
– Neural tube defects (esp valproate 1-2%) and caramazepine (0.51%)
– Orofacial clefts (especially phenytion)
– Cardiac defects (esp phenytion and valproate)
• Minor malformations (fetal anticonvulsant
syndrome)
– Dysmorphic features (V-shaped eyebrows, lowset ears, broad
nasal bridge, irregular teeth)
– Hypertelorism
– Hypoplastic nails and distal digits
Teratogenic Risks of Anticonvulsants
• Little difference in risk levels between drugs
• Risk for any one drug is 6-7% (2-3x↑)
• Risk increases with number of drugs
(polypharmacy)- taking 2 or more: risk 15%
• If take phenytion, valproate AND carbamazepine,
risk to fetus is up to 50%
• Benzodiazepines are not teratogenic
• Mechanism of teratogenesis though to be folate
deficiency
– All women should be on high dose folate (5mg/day)
preconceptually and throughout pregnancy
Management in Pregnancy
• Preconceptually:
• take folic acid 5mg/day from at least 12 weeks prior to conception
• Pregnancy
• Continue folic acid throughout as risks folic deficiency anaemia
• Continue current drugs if well controlled except
• Wean off/change phenobarbitone due to risks of neonatal
withdrawal convulsions
• Detailed fetal scan at 18-20 weeks with detailed fetal cardiac scan
at 22 weeks
• Advise shallow bath or shower (risks of drowning if fit)
• Relatives advised re: recovery position of fits
• If give steroids, ↑dose if enzyme inducing drugs (phenytoin,
phenobarbitone, carbamazepine)
• Vit K 10-20mg orally from 34-36 weeks if on enzyme inducers due
to risks of fetal Vit K deficiency and Haemorrhagic Disease
Newborn
Intrapartum Management
• Most have normal deliveries
– LSCS only if recurrent generalised seizures in late
pregnancy/labour
• Increase in fits around time of delivery
– 1-2% fit during labour
– 1-2% fit within 24 hours delivery
• Continue antiepileptic drugs in labour
• Offer early epidural to reduce pain/anxiety
Postpartum Management
• Neonate should have 1mg IM Vit K
• Encourage to breastfeed
• Advise re shallow baths/showers-door not
locked
• Risks of SUDEP ↑ in pregnancy and postnatal
period
Obstetric Cholestasis
• Disease unique to pregnancy
• 1% in European womenhigher in women from S Asia
• Diagnosis of exclusion
• +ve family history in 33%
• Thought precipitated by high
levels circulating oestrogens
• Can recur with COCP
Diagnosis
• Severe pruritis-limbs and trunk, especially palms
and soles
• Second half of pregnancy (usually 3rd trimester)
• No rash
• LFT are abnormal
• May be associated dark urine, anorexia,
steatorrhoea
• If HCV antibody +ve, onset symptoms earlier
(mean 29/40) compared to HCV –ve (mean
34/40)
Diagnosis
1. Typical history of pruritis without rash
2. Abnormal LFTs
3. Exclusion other causes pruritis and abnormal LFTS
• LFTs
–
–
–
–
Moderate (<3x↑) ALT
Raised GGT (20% cases)
Mild ↑bilirubin (uncommon)
↑total serum bile acids-may be only abnormality
• Pruritis may precede abnormal LFT-serial
measurements advised in women with typical
persistent itching
How to exclude other causes?
• Liver USS (presence of gallstones WITHOUT
extrahepatic obstruction does not preclude D
of OC)
• Viral serology (Hep A, B, C, EBV, CMV)
• Liver autoantibodies
– Anti-smooth muscle Abs for chronic active
hepatitis
– Anti-mitochondrial Abs for primary biliary
cirrhosis
Maternal Risks
• Vit K deficiency
• Increased risk PPH
• Iatrogenic interventions
Fetal Risks
• Intrapartum fetal
distress (12-22%)
• Amniotic fluid
meconium (25-45%)
• Spontaneous preterm
delivery (12-44%)
• Iatrogenic PTD
• Intrauterine death
• Fetal intracranial
haemorrhage
Fetal Risks
• Reduced from 11% PNMR in early studies to 23.5% more recently
• Most recent studies suggest outcomes same to normal
population with treatment
•
•
•
•
Mechanisms of fetal effect not known
Increases towards term
?correlate with serum bile acid levels
Prediction fetal compromise difficult
• No reliable acceptable means (USS, Doppler, CTG)
Management
• Carefully counsel regarding risks
• Regular LFTs and clotting (PT/INR) and BA
• Monitor fetal wellbeing
– CTGs, Dopplers, USS
• Drug treatment
– Vit K, antihistamines, ursodeoxycholic acid (UDCA)
• Early delivery at 37-38 weeks
Drug Therapy
• Vitamin K
• 10mg orally OD –preferably water soluble preparation
• Commence from 32 weeks as risk PTL
• Offer to all
• Antihistamines
• Chlorpheniramine or promethazine may help pruritis
• UCDA
• Reduces bile abids
• Unlicensed in pregnancy but no adverse effects reported
• Evidence lacking to support beneficial effect but widely used
• Dexamethasone
• Can relieve pruritis and lower bile acids-12mg OD orally,
evidence lacking, risks associated with steroid therapy
Intrapartum Management
• If don’t labour spontaneously, induce at 37-38
weeks
• Continuous monitoring in labour as risks fetal
distress
• Neonate should have 1mg IM Vit K at delivery
Postpartum Counselling
• Recurrence risk is 90%
• Avoid oestrogen-containing OCP as may
provoke recurrence symptoms
– If wishes to use, must monitor LFTs
• HRT though does not need to be avoided as
only gives physiological levels oestrogens
Acute Fatty Liver of Pregnancy (AFLP)
• Rare
– 1 in 9000-1 in 13000 pregnancies
• Potentially lethal
– 10-20% maternal mortality
– 20-30% perinatal mortality
• Some consider as variant PET
• Commoner in:
– Primigravidae
– Male fetus 3:1
– Multiple pregnancy
Clinical Features
• Presents after 30/40,
usually near to term
• Gradual onset nausea,
anorexia and malaise
• Severe vomiting and
abdominal pain should alert
to diagnosis
• Often co-existing features
PET but usually MILD
• Jaundice appears within 2
weeks onset and there may
ascites
• LFT abnormal with 310x↑transaminases and
raised AlkP
• Coagulopathy due to DIC
• Associated renal
impairment
• Polyuria and features
diabetes insipidus may
occur (AFLP and DI
assicated)
• May develop fulminany liver
failure with hepatic
encephalopathy
Symptom
HELLP
AFLP
Epigastric Pain
+
+
Hypertension
++
+
Proteinuria
++
+
Elevated liver enzymes
+
++
Hypoglycaemia
+/-
++
Hyperuricaemia
+
+++
DIC
+
++
Thrombocytopaenia (no
DIC)
++
+/-
Raised WCC
+
++
USS/CT
Normal/Haematoma
Normal/steatosis
Multiple pregnancy
+
Primiparous
++
+
Male fetus
50%
70%
Differentiating from HELLP
• See chart
• Profound hypoglycaemia (not invariably
present)
• Marked hyperuricaemia
Management
• Deliver ASAP
• Multidisciplinary team management in ITU
• Treat coagulopathy and hypoglycaemia
aggressively prior to delivery
– Including albumin, FFP, 50% glucose
– May sometimes use plasmapheresis
• Multiorgan failure may require ventilation and
dialysis
• Fulminant hepatic failure and encephalopathy
should prompt transfer to specialist liver unit
– Liver transplantation may be required
Outcomes
• Prompt reversal of clinical and lab findings
usually follows delivery
• Significant morbidity is common
• May need repeated operations to control PPH
due to severe DIC
• If survives, complete recovery without longterm liver damage is the norm
• Recurrence has been described
Any Questions?