Letter to the Editors
org
Antiplatelet therapy before or after 16 weeks
gestation for preventing preeclampsia
TO THE EDITORS: We read with interest the meta-analysis
of Meher et al1 on antiplatelet therapy for the prevention of
preeclampsia. While their results suggest modest benets
from aspirin, we believe the authors should have considered
some methodological limitations and some aspects of peri-
natal diseases mechanisms in their analyses that could have
led them to different conclusions.
Only selected randomized trials published before 2005
were included. At that time, there was little scientic evidence
about the optimal posology of aspirin during pregnancy.
Therefore, most participants were taking only 60 mg of
aspirin daily, which is probably insufcient, and potentially in
the morning when aspirin has minimal effects.2 The results
were stratied according to gestational age (16 weeks) and
dosage (75 mg daily) but the authors did not report the
combination of both (aspirin >75 mg 16 weeks). We
recently demonstrated that the benets of aspirin initiated
16 weeks of gestation was following a dose-response effect
while the benets were modest or absent when aspirin was
initiated >16 weeks.3
The most important point that needs to be addressed is the
selection of outcomes. Most obstetricians will dene preterm
birth (PTB) as a delivery <37 weeks and not <34 weeks.
Recent literature stratied PTB into early onset (<32 or <34
weeks) and late onset (32-36 or 32-36 weeks) because of
evidence showing that mechanisms of disease leading to PTB
are different according to gestational age. Most cases of
spontaneous early-onset PTB are associated with intra-
amniotic infection and inammation and it is biologically
unlikely that 60 mg of aspirin taken daily could prevent such
cases. On the other hand, mechanisms leading to late-onset
PTB are less well understood and it could be interesting to
know whether low-dose aspirin could be benecial. Similarly,
most cases of preterm or early-onset preeclampsia are asso-
ciated with deep placentation disorders that represent a fail-
ure of the physiological transformation of uterine spiral
arteries, which typically occurs <16 weeks of gestation.4 We
previously observed that aspirin initiated <16 weeks was
benecial to reduce the risk of preterm but not the term form
of preeclampsia.5
For the benet of readers and pregnant women, could the
authors provide the relative risks of preterm preeclampsia
(<37 weeks), early-onset preeclampsia (<34 weeks), and PTB
ajog.
(<37 weeks) associated with aspirin started 16 weeks at a
dose >60 or 75 mg? -
Stphanie Roberge, PhD
Suzanne Demers, MD, Msc, FRCSC
Department of Obstetrics and Gynecology
Faculty of Medicine
Universit Laval
Quebec City, Quebec, Canada
Harris Birthright Research Center of Fetal Medicine
Kings College Hospital
London, United Kingdom
Emmanuel Bujold, MD, MSc, FRCSC
Department of Obstetrics and Gynecology
Faculty of Medicine
Universit Laval
Quebec City, Quebec, Canada
emmanuel.bujold@crchudequebec.ulaval.ca
The Canadian Institute of Health Research supported Dr Roberge
(postdoctoral fellowship). The Fond de Recherche du Qubec-Sant
supported Drs Bujold (clinician scientist award) and Demers (MSc award)
during the study. The current study was funded by the Jeanne and Jean-
Louis Lvesque Perinatal Research Chair at Universit Laval, Quebec
City, Quebec, Canada.
The authors report no conict of interest.
REFERENCES
1. Meher S, Duley L, Hunter K, Askie L. Antiplatelet therapy before or
after 16 weeks gestation for preventing preeclampsia: an individual
participant data meta-analysis. Am J Obstet Gynecol 2017;216:121-8.
e2.
2. Ayala DE, Ucieda R, Hermida RC. Chronotherapy with low-dose
aspirin for prevention of complications in pregnancy. Chronobiol Int
2013;30:260-79.
3. Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. The
role of aspirin dose on the prevention of preeclampsia and fetal growth
restriction: systematic review and meta-analysis. Am J Obstet Gynecol
2017;216:110-20.e6.
4. Ogge G, Chaiworapongsa T, Romero R, et al. Placental lesions
associated with maternal underperfusion are more frequent in early-onset
than in late-onset preeclampsia. J Perinat Med 2011;39:641-52.
5. Roberge S, Villa P, Nicolaides K, et al. Early administration of low-dose
aspirin for the prevention of preterm and term preeclampsia: a systematic
review and meta-analysis. Fetal Diagn Ther 2012;31:141-6.
2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.
2017.01.034
MONTH 2017 American Journal of Obstetrics & Gynecology 1