Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study
BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7411.368 (Published 14 August 2003) Cite this as: BMJ 2003;327:368All rapid responses
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Although exposure to magnetic fields during pregnancy was associated
with miscarriage (1), it was not associated with use of NSAIDs.
Therefore, it was not a confounder, and adjustment for exposure to
magnetic fields did not make any difference to the association between
NSAID use and miscarriage. With regard to interviews after miscarriage,
please refer to our previous response to a Letter to the Editor (2). The
bottom line was: had we only included women who were interviewed before
their miscarriage (prospectively ascertained), the association between
NSAID use and miscarriage would have been even stronger.
If Benedetta et al intended to disprove our findings with results
from their “study”, they failed to provide enough information to allow
readers to evaluate their “study”. Based on the limited information they
provided, it is clear that they did not have adequate data to address the
NSAID-miscarriage relationship. First, their study was based on selected
populations (volunteers who used medications during pregnancy and called
the centre). Second, there was no information on miscarriage rates in
their study subjects nor on gestational age at entry for different exposed
groups. In addition, their use of logistical regression which assumes
entry at the time of conception for all study population could result in
biased estimates. Third, it was not clear what was considered NSAID use.
Finally, the fundamental weakness in their study was the comparison group.
Users of other drugs could easily have a higher miscarriage rate than that
in general population simply because of their underlying conditions (e.g.,
depression, reproductive tract infections, etc) or the use of other drugs.
The striking contrast of a strong association between NSAID and
miscarriage, and a lack of association between acetaminophen and
miscarriage observed in our study (3) provides strong evidence against the
argument that NSAID-miscarriage association was due to generic association
with any drug use. Such striking contrast supported by underlying
biological plausibility has laid a solid foundation for the NSAID-
miscarriage association.
Finally, we find that Benedetta et al’s declaration that our finding
“lies on biased data” was not supported by any solid scientific evidence.
Such a strong statement without backing of evidence from better-conduced
studies is neither useful nor constructive.
De-Kun Li
Liyan Liu
Raxana Odouli
Division of Research
Kaiser Foundation Research Institute
Kaiser Permanente
Oakland, California, USA
References
1. Li DK, Odouli R, Wi S, Janevic T, Golditch I, Bracken TD et al. A
Population-Based Prospective Cohort Study of Personal Exposure to Magnetic
Fields during Pregnancy and the Risk of Miscarriage. Epidemiology 2002;
13:9-20.
2. Li DK, Liu L, Odouli R. Authors' Response to "Questions regarding
methodological details. BMJ.com.
3. Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-
inflammatory drugs during pregnancy and risk of miscarriage: population
based cohort study. BMJ 2003;327:368.
Competing interests:
None declared
Competing interests: No competing interests
Li et al have recently reported that use of NSAID in the first half of pregnancy is associated with an 80% increased risk of miscarriage compared with non-users (1).
Based on a case control study we have previously reported similar results (2). At the time of our first analyses we did not have data on gestational age at time of miscarriage.
Since our primary publication we have got access to more recent data from 1998 to 2002 regarding the miscarriages recorded in the hospital discharge registry in North Jutland County. These new data also include gestational age.
Data regarding miscarriage and birth and drug exposure were obtained from the hospital discharge registry and the pharmaco-epidemiological prescription database of North Jutland County as described in detail previously (2).
From the discharge registry we identified a total of 1599 cases of women with first recorded miscarriage, of whom 45 according to the prescription database had filled one or more prescriptions for NSAID in the last 12 weeks before the day of miscarriage.
As controls we used 10 primigravida delivering after 28th gestational week in the same time period (n= 15 990).
Cases and controls were classified as drug exposed if they had been recorded in the prescription database of North Jutland as redeeming prescriptions for NSAIDs at appropriate periods in pregnancy.
In a case control design we analyzed the association between miscarriage and NSAID use stratified in the same five periods before miscarriage as used in our first analyses.
As seen in Table 1 we found a consistently positive association between miscarriage and exposure to NSAIDs in the weeks before miscarriage with odds ratios varying from 3.35 (95% CI 0.88-12.79) to 0.58 (95% CI 0.18-1.85).
Sampling on the specific gestational age substantially reduced the strength of our previously reported association between NSAID use and risk of miscarriage, and we have thus quantified the magnitude of sampling bias when the impact of gestational age is not available. However, the association remains consistently positive in all analyzed time periods with a trend towards a stronger association when looking at the periods closer to the miscarriage. Whether this association is caused directly by NSAID or by the indication for prescribing the drug is still not solved.
Table 1 Without gestational age (from ref. 2) Including gestational age (new analyses) Week of miscarriage Odds ratio 95% CI Cases exp. to NSAID n=1554 Controls exp. to NSAID n =15 677 Odds ratio 95% CI 1 6.99 2.75-17.74 3 8 3.35 0.88-12.79 2-3 3.00 1.21-7.44 5 33 1.50 0.58-3.86 4-6 4.38 2.66-7.20 18 122 1.50 0.91-2.47 7-9 2.69 1.81-4.00 16 100 1.59 0.93-2.70 10-12 1.26 0.85-1.87 3 50 0.58 0.18-1.85
References
1 Li D-K, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs. during pregnancy and risk of miscarriage: population based cohort study. BMJ 2003;327:368-73.
2 Nielsen GL, Sørensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs. a population based observational study and case-control study. BMJ 2001;322:266-70.
Competing interests:
None declared
Competing interests: Table 1 Without gestational age (from ref. 2) Including gestational age (new analyses)Week of miscarriage Odds ratio 95% CI Cases exp. to NSAIDn=1554 Controls exp. to NSAIDn =15 677 Odds ratio 95% CI1 6.99 2.75-17.74 3 8 3.35 0.88-12.792-3 3.00 1.21-7.44 5 33 1.50 0.58-3.864-6 4.38 2.66-7.20 18 122 1.50 0.91-2.477-9 2.69 1.81-4.00 16 100 1.59 0.93-2.7010-12 1.26 0.85-1.87 3 50 0.58 0.18-1.85
SIR-De-Kun Li et al’s paper (
highlights in a confounding way the risk of miscarriage for women using NSAIDs1.
A closer look reveals the weakness of the results.
The study is based on a cohort originally selected
to evaluate exposure to magnetic fields as a risk factor for miscarriage2.
Since a positive correlation was found, this variable should have been included
in the analysis.
Recently the authors published another study3
using the same cohort (and interview). Since at the time of the interview
103/170 women had already had a miscarriage, which could have influenced their
recall of NSAID use, this factor should have been taken into consideration.
Therefore,
considering the widespread use of NSAIDs4, the impact of this
publication and the debate generated, we decided to analyse our data from the
CRIF (Regional Drug Information Centre) performing a cohort study on 1557
pregnant women (gestational age <_20 weeks="weeks" who="who" contacted="contacted" the="the" centre="centre" between="between" _2000="_2000" and="and" _2002.="_2002." each="each" woman="woman" was="was" interviewed="interviewed" after="after" delivery="delivery" for="for" information="information" on="on" pregnancy="pregnancy" outcome.="outcome." in="in" all="all" _281="_281" women="women" were="were" exposed="exposed" to="to" span="span" class="SpellE"/>NSAIDs
(10% aspirin, 90% other anti-inflammatory agents
M01A according to the International Anatomical Therapeutical
Classification Code) and 1276 to other drugs, mainly psychotropics
(11%) and systemic anti-infectives
(10%). The average number of drugs taken was 2.2
(range 1-14).
A
statistically significant association was found for NSAID exposure with a cRR of 1.51 (95% CI,1.11-2.07)
(Table 1), in agreement with De-Kun Li et al’s results (cRR
1.61; 95% CI,0.98-2.65). Moreover, we noticed
a significant trend (c2t=10.54; p=0.0011) for
the number of drugstaken since the last menstruation.
The results of a logistic
regression analysis using a backward stepwise selection, excluding those with a
significance level p>=0.20 and considering the variable
“number of drugs” as continuous, showed that there is a significant
association between
the number of drugs taken and the risk for spontaneous abortion
(OR 1.15; 95% CI,1.06-1.25) but not between NSAID use and the latter. This underlies the importance of including such a variable, even
though it was not considered a confounding factor in the previous studies.
Thus, once again, there is a lesson to be
learned concerning the interpretation of available data. In this case, scant
and weak methodological approaches indicated exposure to NSAIDs
early in pregnancy as a substantial risk factor for miscarriage, but only a
larger, collaborative, multinational and well-designed study can produce more
concrete evidence.
Schiavetti Bendettaresearchfellow, Antonio Clavenna senior
researchfellow,
Rita Campi statistician,
Maurizio Bonati head.
Laboratory for Mother and Child Health and CRIF-Regional Drug
Information Centre, Mario Negri Institute for Pharmacological Research, 20157
1. De-Kun Li, Liu L, Odouli
R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk
of miscarriage: population based cohort study. BMJ 2003; 327:368-372.
2.
De-Kun Li, Odouli R, Wi
S, Janevic T, Golditch I,
Bracken TD, Senior R, Rankin R, Iriye R. A population-based prospective cohort study of personal exposure to
magnetic fields during pregnancy and the risk of miscarriage.Epidemiology 2002;13
(1):9-20.
3.
De-Kun
Li, Janevic T, Odouli R,
Liu L. Hot tube use during pregnancy and the risk of miscarriage. Am J Epidemiol 2003;158:931-9374.
4.
Collaborative
Group on Drug Use in Pregnancy (C.G.D.U.P.). Medication during pregnancy: an intercontinental
cooperative study. Int J GynaecolObstet 1992;39(3):185-96.
Table1. Univariate analysis of spontaneous abortion risk (percent;
absolute values are in parentheses ) related to
characteristics of the women (n=1557).
* p0.05 |
Competing interests:
None declared
Competing interests: No competing interests
I am writing in response to your study regarding use of NSAIDS before
and during pregnancy.
I am a 31 year old whom has recently had two
consecutive early first trimester losses. Both pregnancies were conceived
with the use of Clomid 50mg dose. The first loss occurred at 8 weeks
after the first cycle of Clomid, and the second loss occurred at 5.5 weeks
after the third cycle of Clomid. Due to a medical history of chronic
abdominal pain cause by a splenectomy and partial pancreatectomy secondary
to a non-functioning islet tumor on the distal tail. Leaving me with
adhesions throughout my abdomen. I use ibuprofen on a daily basis usually
at high doses to control the pain, up to 5000mg daily.
During both
pregnancies I was using ibuprofen up until I confirmed pregancies (approx.
2 weeks gestational age), as well as preconception. I was tested for all
the routine causes after the second loss and all were negative.
I am
concerned that other women may be self medicating as I was and unknowingly
be causing their own miscarriages. This study has been televised in my
state of Georgia, but I am fearful that it is not well known knowledge
throughout the OB/GYN community or believed. Speaking for myself if there
is a small chance that NSAID usage caused my miscarriages that is enough
for me to discontinue any usage preconception or during preganancy. I
will giving a copy of your study to my OB Physician in hopes that it my
help another woman from suffering a unneccessary loss. I would like to
personally thank you for taking the time to create a study to spotlight
NSAID usage in pregnancy.
Competing interests:
None declared
Competing interests: No competing interests
Li, et al. suggest that commonly used medicines (non-steroidal anti-
inflammatory drugs; NSAIDs and aspirin) increase the risk of miscarriage.1
Their study, however, suffers from methodological flaws and ambiguities of
interpretation.
Selection bias existed from the outset; only those who spoke English
and intended to carry the pregnancy to term were deemed eligible. Spoken
language may represent a proxy indicator for socio-economic status in the
study locality; while the intention to carry the pregnancy to term may be
related to general health. Poor socio-economic and general health
conditions can have a profound effect on the outcome of pregnancy
including miscarriage.
Self-exclusion may have played an even greater role in determining
the characteristics of those included in the study and ultimately its
outcome. Of 2729 eligible women, only 1063 (39%) participated. Non-
participation may be a function of poor socio-economic conditions.
Alternatively, women who have already miscarried may not be prepared to
participate in a study of pregnancy outcome reflecting certain cultural or
educational backgrounds.
The authors have demonstrated that among the study groups, women of
higher socio-economic status were more likely to have used NSAIDs. Since
both selection bias and self-exclusion have probably served to under-
represent women of lower socio-economic status, the final conclusions are
likely to have been unrepresentative of the true outcome in the community
at large.
The authors correctly identified a number of factors which can vary
the risk of miscarriage between NSAIDs and aspirin users and non-users.
Thus, users of NSAIDs and aspirin were more likely to have been of a
particular race, older, had two or more prior miscarriages, more prior
pregnancies and to have drunk coffee and alcohol or smoked since their
last menstruation than non-users of the medicines in question. We were
told that “after adjustment” for some of these factors there was an 80%
increased risk of miscarriage associated with the use of NSAIDs during
pregnancy. However, the manner and the magnitude of the adjustment was not
explained.
The authors have also correctly identified the possibility that the
condition for which NSAIDs or aspirin was taken might cause miscarriage,
rather than the drugs themselves. Their attempt to adjust for this
confounding factor consisted of merely excluding women who reported cramps
as the reason for taking NSAIDs or aspirin. The authors failed to exclude
women who took NSAIDs and aspirin because of symptoms of infections, auto-
immune and connective tissue disease. Such conditions are known to be
associated with increased risk of miscarriage.
My final criticism of this paper is related to its title and the
confusion it causes among many patients and their physicians alike. The
final conclusion was “Prenatal use of NSAIDs and aspirin increased the
risk of miscarriage”. However, the title cited the risk period of exposure
as “during pregnancy”. This was probably a reflection of lack of
presentational clarity rather than an intentional widening of remit of
applicability. A precise definition of the risky period for exposure to
NSAIDs and aspirin, if it indeed exists, could not be more critical
particularly for patients with anti-phospholipid syndrome. Aspirin is
prescribed to such patients from early pregnancy onwards specifically to
reduce the risk of repeated miscarriages.2 According to the authors’
suggested pathophysiology, the intake of aspirin is associated with an
increased risk of miscarriage at the implantation stage. Once pregnancy is
established and diagnosed, the risk of miscarriage for such patients is
likely to be greater, if aspirin is withheld.
1. Li D-K, Liu L, Odouli R. Exposure to non-steroidal anti-
inflammatory drugs during pregnancy and risk of miscarriage: population
based cohort study. BMJ 2003; 327: 368-72.
2. Rai R., Cohen H., Dave M., Regan L. Randomised controlled trial of
aspirin and aspirin plus heparin in pregnant women with recurrent
miscarriages associated with antiphospholipid antibodies BMJ 1997; 314:
253-7.
Competing interests:
None declared
Competing interests: No competing interests
The following are our responses to the four questions raised by
Klebanoff et al:
1. In our recently published paper (1), readers were referred to a
previous publication for detailed methodological issues (2). With regard
to potential recall bias due to knowledge of miscarriage, if we excluded
those women who were interviewed after their miscarriage, the association
between NSAID use during pregnancy and the risk of miscarriage would have
in fact been even stronger (hazard ratio=3.2, 95% confidence interval: 1.5
-7.0). In other words, had we only included women who were interviewed
prospectively (before the end of their pregnancy), we would have
demonstrated a greater risk of miscarriage associated with NSAID use
during pregnancy. This finding provides no evidence to support the
argument of recall bias.
2. The association between timing of NSAID use and the risk of
miscarriage was based on participants’ response to the question: “when did
you start to take this medication (gestational age in weeks)”after they
answered “yes” to the question about use of any medications during
pregnancy. While the accuracy of gestational age in this case may be
difficult to measure, any speculation on reporting bias would need to
explain the striking contrast of the effect between NSAID/aspirin and
acetaminophen use observed in our study both of which were based on the
same question.
3. Women who are treated with assisted reproductive technology at
infertility clinics are not representative of the general population of
pregnant women. Many of them have underlying conditions resulting in
infertility that may well benefit from treatment of low-dose aspirin. For
example, studies have shown that antiphospholipid antibody syndrome (APS)
and thrombosis increases the risk of multiple miscarriages and
infertility, and treatment with low-dose aspirin together with heparin may
lead to a higher rate of successful pregnancy than that without treatment
(3-6). However, this benefit could be due to either (a) lower dose
aspirin used in the treatment or (b) the benefit of treating the
underlying condition (APS) (a relative risk of 3-5 for miscarriage)
outweighs the risk of aspirin use itself (a relative risk of 1.6).
Finally, women with APS only account for less than 0.5% of all pregnant
women and we did not have any women use NSAIDs or aspirin for APS in our
study population.
4. While it is true that the hazard ratio for the overall association
between NSAID use and miscarriage was only borderline significant, our
conclusion was not solely based on this single piece of statistics; rather
our conclusion was based on multiple pieces of evidence that were
presented in our paper. In addition to the overall association, the
greater risk associated with use around the time of conception (biological
plausibility) and with longer duration (dose-response relationship), and
striking contrast of the effect between NSAIDs/aspirin and acetaminophen
use (biological plausibility) are all coherent pieces of evidence
supporting the same conclusion. In addition, the new class of COX-2
NSAIDs [celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra)]
have been classified by FDA as Pregnancy Category C (generally should be
avoided during pregnancy unless benefits outweigh the risk) because Cox-2
NSAIDs have been shown to cause peri-implantation and post-implantation
losses and to reduce embryo/fetal survival in rats and rabbits due to
their inhibition of prostaglandin synthesis (7). Therefore, our findings
are consistent with previous findings from both human and animal studies.
Reference
1. Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-
inflammatory drugs during pregnancy and risk of miscarriage: population
based cohort study. BMJ 2003;327:368.
2. Li DK, Odouli R, Wi S, Janevic T, Golditch I, Bracken TD et al. A
Population-Based Prospective Cohort Study of Personal Exposure to Magnetic
Fields during Pregnancy and the Risk of Miscarriage.
Epidemiology.2002.Jan.;13.(1.):9.-20.13:9-20.
3. Cucurull E, Gharavi AE, Menon Y, Wilson WA. Antiphospholipid
Antibody Syndrome. Curr.Treat.Options.Cardiovasc.Med. 2003;5:127-36.
4. Galli M,.Barbui T. Antiphospholipid syndrome: definition and
treatment. Semin.Thromb.Hemost. 2003;29:195-204.
5. Lee RM,.Silver RM. Recurrent pregnancy loss: summary and clinical
recommendations. Semin.Reprod.Med. 2000;18:433-40.
6. Roubey RA. Treatment of the antiphospholipid syndrome.
Curr.Opin.Rheumatol. 2002;14:238-42.
7. Physicians' Desk Reference (PDR). Montvale, NJ: Medical
Economics Company, 2002.
Competing interests:
None declared
Competing interests: No competing interests
To the Editor:
Li, et al.(1) raise the troubling possibility that a commonly used group of drugs might increase a
woman's risk of miscarriage.(1) However, the authors do not provide some important
methodologic details critical for interpreting this provocative finding.
First, although the authors note that most women were still pregnant when interviewed, they do
not say specifically whether most women who experienced a miscarriage were interviewed
before or after the event. Mundane, intermittent exposures such as taking a non-steroidal drug
for a headache are particularly susceptible to biased recall,(2) so knowledge of the fraction of
cases interviewed while still pregnant is of great importance in assessing the credibility of the
results.
Second, tables 2 through 4 show that virtually all of the association was accounted for by use
beginning in "the first week of gestational age." Use beginning later in pregnancy did not carry
a statistically or practically significant increase in risk. Are the authors referring to
embryological or obstetrical gestational age? The latter poses difficulties in interpretation, since
a woman does not normally ovulate until approximately gestational week two, and does not miss
her menstrual period until the end of week 4. Are the authors claiming that use of these drugs
one to two weeks before ovulation can cause miscarriage?
Third, these results appear to be at variance with assisted reproductive technology practice, where
randomized clinical trials have shown that early aspirin use results in at worst no lower(3) and at
best higher (4) pregnancy success rates.
Finally, we note that the lower confidence limit of the overall association between non-steroidal
drugs and miscarriage was 1.0. Therefore, this result was on the borderline of statistical
significance.
In summary, without knowing when the women experiencing miscarriage were interviewed
given the potential for biased recall, coupled with questionable gestational duration, uncertain
biological plausibility and a confidence interval that may include 1.0, we believe that the results
of Li, et al. are overstated.
References:
1. Li D-K, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during
pregnancy and risk of miscarriage: population based cohort study. BMJ 2003;327:368-72.
2. Rockenbauer M, Olsen J, Czeizel AE, Pedersen L, Sorensen HT. Recall bias in a case-control
surveillance system on the use of medicine during pregnancy. Epidemiology. 2001;12:461-6.
3. Urman B, Mercan R, Alatas C, Balaban B, Isiklar A, Nuhoglu A. Low-dose aspirin does not
increase implantation rates in patients undergoing intracytoplasmic sperm injection: a
prospective randomized study. J Assist Reprod Genet. 2000;17:586-90.
4. Weckstein LN, Jacobson A, Galen D, Hampton K, Hammel J. Low-dose aspirin for oocyte
donation recipients with a thin endometrium: prospective, randomized study. Fertil Steril. 1997;
68:927-30.
Competing interests:
None declared
Competing interests: No competing interests
The significant higher rate of miscarriage with the use of anti-
inflammatory drugs especially aspirin during per-conceptional period poses
a serious question over the use of aspirin to prevent recurrent
miscarriage which was never proven to be effective for recurrent
miscarriage including for anti-phospholipid syndrome. The study highlights
the importance of age old advice for women not to use any medication
during second half of menstrual cycle to avoid the use of any medication
in this part to avoid their use during the time when conception may have
occurred as it will only be known when the lady will miss her period.
Hence all women who can fall pregnnt should avoid the use of all
medications including over the counter medicines in periconceptional
period unless they are absolutely necessary. The study also highlights the
importance of using standard and time tested medicines like paracetamol
for any indication during this period. Newer and untested medicines during
pregnancy should be avoided in second half of cycle to avoid any
miscarriage or other complications due to their use.
Competing interests:
None declared
Competing interests: No competing interests
I suppose I am one of the patients in which Li, Liu and Odouli's
article has induced, perhaps unnecessary, anxiety! I am currently
undergoing IVF treatment, for which the clinic prescribes low-dose aspirin
to all patients from the time of starting FSH injections until a positive
pregnancy test. The use of low-dose aspirin is supposed to >enhance<
implantation. Now this study comes out, seeming to say just the opposite.
I find it frustrating that the article, which is being picked up heavily
in the media internationally, says nothing about how many of the women
used low-dose aspirin and the impact of this on miscarriage. Surely the
authors were not unaware of the widespread use of low-dose aspirin by
women and by clinics.
I might also be described as one of the women who self-prescribes low
-dose aspirin, because I have already been taking it for several months--
however it was also recommended to me, somewhat informally, by both my
OB/GYN and rheumatologist (I have Undifferentiated Connective Tissue
Disease, and quite elevated ANA, though, significantly NOT elevated Anti-
Phospholipid Antibodies). Mr. Tucker should be aware that low-dose aspirin
is being widely suggested to patients for other indications than
documented Anti-Phospholipid Syndrome.
I wonder if the authors of this study could respond to Ms Maclean's
inquiry about low-dose aspirin specifically.
Competing interests:
None declared
Competing interests: No competing interests
One burning question
I have carefully read your article, as a patient and a scientist, but
not an expert in this field.
The article was brought to my attention by a hematologist, who
instructed me to go off baby aspirin and switch to heparin at 11 weeks
gestation. He heard about it on the news. I doubt he's read it, but I'll
make sure he does.
I was diagnosed with low Protein S and have been taking baby
aspirin daily (starting 2 weeks after conception). This pregnancy, so
far, is working (after four miscarriages we've seen a hearbeat at 7, 8 and
10 weeks, and the baby is measuring fine with good activity), and I was a
bit leary about discontinuing the baby aspirin and completely switching to
the heparin in light of "fixing something which is not broken". (I also
have a subchorionic bleed that I hope does not get worse due to heparin)
Which brings me to my question...in Table 3, have the five patients
who miscarried in the categories of using aspirin "at conception" (3
miscarriers) or ">1 week" (2 miscarriers) miscarried in the past? The
text indicates that you corrected for this, but how? Were patients who
miscarried in the past (for either known or unknown reasons)specifically
excluded in these categories? If not, I would think many of those five
taking aspirin (probably baby aspirin-BA) either at conception or for over
a week were miscarriers, like myself, who were instructed to take BA as a
precaution, but perhaps miscarried for completely different reasons (my
husband also carries a balanced translocation, which has caused at least
one of our miscarriages).
Even if these patients were excluded, I think it's a shame that
clinicians may now instruct patients who could benefit from BA (for
anitphospholipid syndrome, for example) to go off of it because of a study
that included only 5 or 6 patients in each of these two categories ("at
conception" or "> 1 week") I've been out of the lab a while, but this
seems like a really low population sample (which also might be self-
selected for multiple miscarriers?). The confidence intervals are large
too. I plan to continue to take the BA in light of the randomized
clinical studies which have indicated that it may be helpful in
conjunction with heparin for people like me.
Competing interests:
None declared
Competing interests: No competing interests