Transcript Intrauterine Growth Restriction

Fetal Growth
in pregnancies affected
by substance misuse
Objectives
• Examine association of substance abuse with
fetal growth problems
• Identify commonly used illicit substances and
their effect on fetal growth
• Fetal surveillance in pregnancies with
substance misuse
• Interventions to improve fetal outcome
•Small babies contribute disproportionately to perinatal morbidity
and mortality
•The main contributor to this association is FGR rather than SFD
•The increased morbidity and mortality is a result of intrauterine
hypoxia, acidaemia, prematurity (often iatrogenic) and neonatal
complications
Does substance misuse affect
fetal growth?
Does substance misuse affect
fetal growth?
Scottish drug misuse statistics report normal birth
weight in >75% of women who report substance
misuse
Reported weight deficit
•Smoking: Both active and passive smoking are associated with a
significant weight deficit (460 g and 200 g respectively)
•Marijuana: 79 g
•Heroin: 489 g
•Methadone: 279 g
•Combined Methadone and Heroin: 557 g
Substance misuse may be
associated with FGR, but are illicit
drugs?
Substance misuse IS associated
with FGR, but are illicit drugs?
It remains difficult to prove an independent
effect on fetal growth for most common
substances.
Do illicit drugs affect fetal growth?
•Studies are fraught with difficulties
•Not possible to conduct trials
•Data largely from epidemiological studies and animal
models
•Lots of confounding variables
Socioeconomic factors/poverty
Domestic violence
Legal drugs Smoking/alcohol
Multiple illicit drugs
Nutrition
Associated health issues
LBW often 2o to prematurity
How can illicit drugs affect fetal growth?
• Normal small
• Abnormal small
• Infected small
• Starved small
• Wrong small
Cocaine
•Inhibits presynaptic uptake of sympathomimetic neurotransmitters including
norepinephrine, serotonin and dopamine
•Hypertension, tachycardia and myocardial ischaemia
•Rapid transfer across the placenta to the fetus by simple diffusion; may cause
significant vasoconstriction of fetal blood vessels. Indirect fetal effects of
cocaine result from maternal vasoconstriction.
•Since uterine blood flow is not autoregulated, decreased blood flow may lead
to uteroplacental insufficiency, acidosis and fetal hypoxia
•It is associated with villous haemorrhage even in the absence of abruption
Amphetamines
•Indirect acting sympathomimetic drugs, that produce powerful central nervous
system stimulation with peripheral α and β-adrenergic receptor actions
•Result in euphoria, increased cortical alertness, decreased fatigue and
appetite suppression.
•Clinically indistinguishable from effects caused by cocaine. Hypertension,
arrhythmias, tachycardia, dilated pupils, hyperreflexia, proteinuria, and
confusion have all been reported.
•Adverse pregnancy outcome with prenatal exposure to amphetamines:
Congenital malformation, FGR, IUD and cerebral haemorrhage have been
reported.
•Targets noradrenalin and serotonin transporters in the placenta
Marijuana (THC)
•THC crosses the placenta freely and has a direct effect on the
fetus
•FGR occurs largely in mice
•No obvious effect on placenta
•Confounded by the fact that it is usually smoked with tobacco
Smoking
•Smoking increases resistance in the umbilical artery, and may
reduce intervillous blood flow
•Nicotine impairs placental nutrient transfer
•Carbon monoxide impairs oxygen delivery to the fetus by
displacing oxygen from maternal haemoglobin, and diminishes
oxygen carrying capacity of fetal blood
Opiates
•Intravenous opioid abuse in pregnancy may affect the fetus indirectly
(e.g. maternal malnutrition or infection) or directly (e.g. transplacental
opioid transfer). FGR and fetal distress are described consequences
of opiate addiction.
•Increased permeability of placenta, particularly where Heroin
combined with Methadone.
Other
•Benzodiazepines- some effect on growth described but no clear
mechanism, more concerns about teratogenicity
•MDMA- no data on growth to date
•Volatile substances- prematurity
Antenatal surveillance
• Given the association between substance misuse in
pregnancy and low birth weight, antenatal fetal
surveillance should follow principles of high risk
pregnancy care
• Serial ultrasound & Doppler assessment of the fetus
should be offered
• This will allow:
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Early diagnosis of at risk/small fetuses
Utilising intensive surveillance where required
Avoiding unnecessary intervention where fetal assessment is normal
Planning timing/mode of delivery
Antenatal surveillance
Considerations
• One size doesn’t fit all- some patients will be higher risk than others
• Patients misusing vasoactive substances may have significant
placental disease- expected timelines of deterioration may not apply
• Compliance- pragmatic approach to timetable, may need to be
opportunistic; accurate dating may be difficult
• Complacency- remember other causes for FGR
• Anomalies- some drugs used in first trimester may be
teratogenic/vascular disruption etc
Antenatal surveillance
Example fetal growth surveillance plan for a high risk
pregnancy:
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Routine dating USS in first trimester (± nuchal translucency)
AFP in second trimester (additional risk factor)
Detailed USS at 20 weeks + uterine artery Doppler
Serial growth scans at 28-32-36 weeks gestation, looking at centile
position AND velocity of AC/EFW, also including HC (risk of
microcephaly), AFI, UMA
• If any abnormal findings, need to adapt frequency/perform additional
assessments
Diagnosis
1.
Abdominal palpation:
-detects as few as 30% of SFD’s
2.
SFH measurement:
-sensitivity 27%, specificity 88%
3.
Ultrasound anthropometry:
-abdominal circumference and estimated fetal
weight predict SFD (AC 95%, EFW 90%)
-10th centile best predictive threshold
-charts should be customised
-velocity should be used in addition to size
4.
Amniotic fluid volume:
-poor predictive value in diagnosis, but useful
surveillance tool
What surveillance is best?
Umbilical artery Doppler should be the primary
surveillance tool
A recent meta-analysis of18 studies (10,000 women) demonstrated
that in high-risk pregnancy including FGR the use of Doppler
ultrasound is associated with:
•a reduction in perinatal deaths
•fewer inductions of labour
•fewer caesarean sections
•no difference in operative vaginal deliveries
•no difference in Apgar scores <7 at five minutes.
Alfrevic et al (2010)
Surveillance if Umbilical Artery Doppler is normal
•There is no benefit in twice weekly Doppler
•Twice weekly Doppler results in earlier intervention without clear benefit in
terms of morbidity/mortality
•Biophysical profile is of no proven benefit
•CTG is not associated with better fetal outcome
Surveillance if Umbilical Artery End Diastolic Flow is
absent or reversed
•Optimal surveillance strategy is not clear
•Interval between first occurrence of AEDF and abnormal CTG/BPP ranges
from 1-26 days
•Admit and administer antenatal steroids
•Additional Doppler assessment
•BPP has good negative predictive value
•Daily CTG
•Consider delivery if gestation >34/40
Doppler parameters
Umbilical artery (UMA):
•End-diastolic flow velocity (normal, reduced, absent, reversed) reflects
increases in placental resistance
•Essential in surveillance of the growth restricted fetus
Middle Cerebral Artery (MCA):
•Represents downstream resistance in cerebral microcirculation
•MCA resistance is normally high throughout gestation, with increasing
flow in the third trimester
•Increased diastolic flow signifies onset of circulatory changes in response
to placental disease
Venous Dopplers
•Information about the ‘pump’
•Candidate vessels include IVC, UVC, and hepatic veins
•The ductus venosus is probably the vein of choice
•Waveform deterioration precedes, and strongly predicts, changes in BPS
requiring delivery
Timing and mode of delivery
Delivery
• When umbilical artery Doppler is normal, delay delivery until at least
37 weeks (in the presence of satisfactory additional assessment)
•With AREDF consider delivery if gestation >34/40 even in the
presence of normal additional assessment
•With AREDF, deliver before 34/40 if CTG abnormal, BPP abnormal, or
other Doppler parameters are abnormal (MCA, umbilical vein)
•Mode of delivery will depend on gestation, presentation, fetal
condition and maternal factors
•Caution with postmaturity
Interventions to improve outcome
• Poor evidence on effectiveness of antenatal support and
treatment programmes from UK and US studies- largely
comparable outcomes for all study groups (see NICE guidance).
However, small numbers and methodological problems.
•One larger US study of approx 7000 women demonstrated
improved outcomes in terms of gestation and weight at delivery
with antenatal support and treatment.
•On balance, women are likely to have better continuity of care
and access health care more readily with dedicated services.
Summary
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Whilst there is insufficient evidence that illicit drugs have a direct impact on
fetal growth, women misusing substances often have multiple and complex
social and medical risk factors for FGR
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Pregnancies associated with substance misuse are known to have a greater
risk of perinatal morbidity and mortality
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Aside from an enhanced package of antenatal care, intensified fetal
surveillance should be offered, including serial fetal growth assessments in the
second and third trimester
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Where a growth deficit is identified, Doppler should be the primary surveillance
tool
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Mode and timing of delivery will largely depend on fetal condition, gestation
and maternal factors
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More data are needed to assess whether enhanced antenatal care results in
improved fetal growth