This document discusses the use of low dose aspirin in obstetrics. It covers the safety, mechanism of action, and various uses of LDA including: prevention of preeclampsia, IUGR, preterm labor, hypertension in multiple pregnancies, and recurrent miscarriage. It finds that LDA is generally safe for mothers and fetuses. It effectively prevents preeclampsia and other adverse outcomes in high-risk pregnancies without major safety risks. The mechanism of action involves diminishing platelet thromboxane A2 synthesis while maintaining prostacyclin synthesis. Guidelines recommend LDA for women with certain risk factors starting between 12-16 weeks.

1. low dose
Aspirin
in obstetrics
Aboubakr
Elnashar
Benha University
Hospital, Egypt
Aboubakr Elnashar

2. Contents
I. SAFETY
II. Mechanism of action
III.USES:
1.Prevention of
1.PET
2. IUGR
3.PTL
4.hypertension in multiple pregnancy
5.repeated miscarriage
6.DVT
2.Treatment of antiphysolipid syndrome
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3. I. SAFETY
Fetal and neonatal complications
stillbirths, neonatal death, birth defects:
Similar
(Ahren et al, 2016).
No increased risk of hemorrhage
either before or after delivery
(HR: .57, 95% CI: .25-1.33; p = .194).
(Ayal et al, 2013)
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4. SCH
LDA: 40.2%
Control: 10.9%
LDA may be associated with an increased risk of
developing a SCH during the first trimester.
(Truong et al, 2016)
Vaginal bleeding:
LDA: 22%
Control: 17%, P=0.02
(Ahren et al, 2016).
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5. Placental abruption
LDA increases the incidence of placental
abruption
(OR, 1.35; 95% CI, 1.05-1.73)
not other major complications
LDA is effective in preventing:
PET
PTL
IUGR
in high-risk pregnancies without posing a
major safety risk to mothers or fetuses.
(XU et al, 2015)
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6. No adverse effects on infants
Decrease behavioral difficulties
(Vinod et al, 2009)
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7. Aboubakr Elnashar

8. II. MECHANISM OF ACTION
diminishes platelet thromboxane A2 synthesis
maintaining vascular wall prostacyclin synthesis:
altering the balance in favor of prostacyclin
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9. Aboubakr Elnashar

10. III. USES
1. Prevention of PET
Rationale
PE:
increased platelet turnover
increased platelet derived thromboxane levels
LDA:
diminishes platelet thromboxane A2
synthesis while
maintaining vascular wall prostacyclin
synthesis: altering the balance in favor of
prostacyclin
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11. I. Studies on moderate and high risk women
low dose aspirin: effective
modest reduction in risk of
PE (0-3% in treated vs 12-35% in controls)
other adverse pregnancy outcome:
PTL, IUGR (by 10-20%).
[Dekker et al, 2001].level 2 evidence (Cochrane SR, 2007 )
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12.  When to start?
≤16 w, at 12 w
significant reduction in:
PE
(RR 0.47, 95% CI 0.360.62; 7.6 vs 17.9%)
 severe PE
(RR 0.18, 95% CI 0.080.41; 1.5 vs 12.3%)
IUGR (RR 0.46; 8.0 vs 17.6%)
PTL
(RR 0.35, 95% CI 0.220.57; 4.8 vs 13.4%)
[Roberge et al, 2013; Meher et al, 2013; XU et al, 2015; Roberge et al,
2016}
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13. Dose:
75-80 mg seems to be the right dosage for about
two thirds of the women
[Rey et al, 2011]
1/3: need higher dosages up to 160 mg
Aspirin resistance test:
woman is resistant to 75-80 mg: increase the
dose.
(Bujold, 2013)
100 mg/d should be the minimum dose for
prevention of complications in pregnancy
(Ayal et al, 2013)
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14. Aspirin non-responsiveness= Aspirin
resistance= Aspirin treatment failure
Significant proportion of aspirin-treated
individuals exhibit suboptimal platelet response
inability of aspirin to reduce platelet
production of thromboxane A2 and thereby
platelet activation and aggregation.
Determination:
Measurements of
whole blood TXA2 formation
urinary excretion of TXA2 metabolites
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15. Causes
inadequate dose
drug interactions
genetic polymorphisms of COX-1 and other
genes involved in thromboxane biosynthesis
upregulation of non-platelet sources of
thromboxane biosynthesis
increased platelet turnover.
can be overcome by
treating the cause or causes
 minimising thromboxane production and activity
blocking other pathways of platelet activation.
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16.  At bed time:
 Not upon awakening
 significantly regulates ambulatory BP
 reduces the incidence of
 Preeclampsia
 gestational hypertension
 preterm delivery, and
 IUGR.
(Ayal et al, 2013)
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17. II. Unselected nulliparous women
little or no benefit
[Sibai et al, 1993]
no effect on incidence of FGR, or length of
gestation
[Subtil et al, 2003].
1. Although nulliparity is a risk factor for PE,
prevalence rates are relatively low (4%)
compared with moderate to high risk groups
(8-30%)
[Henderson et al, 2014].
2. Pathogenesis of PE in nulliparous is
different from that in women with previous
PE or preexisting vascular disease
[Sibai et al, 2005].
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18. III. Studies on women with abnormal uterine artery
Doppler (UAD)
Abnormal UAD: identified women who are likely
to develop PE and IUGR
[Subtil et al, 2003].
PE: 6 vs 1%
IUGR: 18 vs 8%
LDA of abnormal UAD:
Did not reduce the incidence of PE
PE occurred in 2% of patients in each group.
Did not reduce the incidence of IUGR.
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19. Guidelines
ACOG, 2013
LDA:
not recommended for women at low risk for
PE.
Recommend in high risk women: women
with history of :
early onset PE
superimposed PE plus delivery at <34 w
or
PE in >1 pregnancy.
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20. NICE, 2010
low dose (75 mg) aspirin for
 1 high risk factor for PE
chronic hypertension
kidney disease
diabetes
autoimmune disease
hypertension in previous pregnancy OR
2 moderate risk factors for PE
age ≥40 y
first pregnancy
multiple gestation
>10 y between pregnancies,
BMI≥35 kg/m at presentation
family history of PE
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21. US Preventive Services Task Force (USPSTF)
2014
LDA:
≥1 high risk factors
absolute risk for PE ≥ 8%.
{No validated methods (biomarkers, clinical
diagnostic tests, medical history) for identifying
women at high risk for PE}
81 mg/d
at 12 w
Discontinue
5 to 10 days before expected delivery
{diminish the risk of bleeding during delivery}
[Hirsh et al, 2008}
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22. 2. Prevention of IUGR
LDA:
effective in preventing SGA birth in women at
high risk of PET although the effect size is small
(RR 0.51, 95% CI 0.28–0.92)
number needed to treat = 10 (95%CI 5–50).
should be commenced at, or before, 16 w of
pregnancy.
(NICE, 2011)
It is not possible to determine to what extent the
effect of LDA is due to the reduction of pre-
eclampsia in these women.
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23. LDA:
Started
early pregnancy
reduces the risk of placenta-mediated
complications such as IUGR and perinatal
death
after 20 ws:
not effective in reducing the risk of a SGA
infant.
Efficacy has been demonstrated in:
abnormal first-trimester uterine artery Doppler
Prior history of chronic hypertension or PET
(Roberge et al, 2016)
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24. 3. Prevention of PTL
LDA
started early in pregnancy in high-risk women:
prevent more than half of PET and IUGR
significant decrease of PTL
(relative risk 0.22, 95% confidence interval: 0.10-0.49).
(Bujol et al, 2011)
could become an additional weapon in the
prevention of PTL
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25. LDA:
Started at 15 and 18 w
In singleton pregnant women, who had
unexplained AFP >2.5 MOM
reduces
adverse pregnancy outcome
delivery before 34 w
(Khazardoos et al, RCT, 2014)
Preconception LDA:
not significantly associated with the overall rate
of PTL
(Silver et al, 2015)
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26. 4. Prevention of adverse pregnancy outcome In
multiple pregnancy
LDA:
75 mg daily from 12 w until the birth of the babies
if they have one or more of the following risk factors
for hypertension:
1. first pregnancy
2. age 40 years or older
3. pregnancy interval of more than 10 y
4. BMI of 35 kg/m2 or more at first visit
5. family history of PET.
(NICE, 2011)
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27. 5. Prevention of RM
Preconception initiated LDA:
1-2 previous losses:
no significantly associated with live birth or
pregnancy loss
Single documented loss at less than 20 ws during
the previous year:
higher live birth rates
Not recommended for the prevention of pregnancy
loss
(Schisterma et al, 2014; Mumfor et al, 2016)
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28. Preconception-initiated LDA
history of 1-2 pregnancy losses:
non significant increase in fecundability of
14%
history of only one pregnancy loss of <20 w in
the preceding year:
significant increase of 28%
Preconception-initiated LDA may increase
fecundability in certain women with a recent
early pregnancy loss
(Schisterma et al, 2015)
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29. LDA+ LMWH:
No reduction in pregnancy loss rate in pregnant
women with 2 or more consecutive previous
pregnancy losses.
(SPIN (Scottish Pregnancy Intervention) multicenter, RCT; Clar
et al, 2010)
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30. 6. Prevention of thrombosis
Not recommended in:
Any patient group
(American College of Physicians)
Obstetric patient:
(RCOG, 2015)
Postoperative
(NICE,2013)
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31. 7. Treatment of APAS
Improvement of fetal outcomes in APAS
LDA
in combination with heparin is the first line
treatment
(MRCOG, 2011)
-Success:
70%
(Rai et al,1997)
-Reduces the miscarriage rate by
54%
(Empson et al, Cochrane Database Syst Rev, 2005)
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32.  Baseline nonpregnant studies of aPLs:
 CBC with platelets
 PT, PTT
 LA, aCL and aβ2GP
LDA:
75-81 mg:
initiated before conception
discontinued 4 ws before EDD
resumed postpartum
continued for life unless otherwise contraindicated
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33. Thanks
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