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Aines embarazadas

Aines embarazadas

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Published by: maykamen2 on Sep 09, 2011
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N
onaspirin nonsteroidal anti-infammatory drugs (NSAIDs) are oneo the most commonly used medicationsduring pregnancy (17%).
1
Nevertheless, gesta-tional use o nonaspirin NSAIDs remains contro-versial, partly due to the inconsistency o resultsrom studies on their potential risks, the potentialor residual conounding by comorbidities andthe lack o data on the risks associated with spe-cic types and dosages.
1–5
The strongest associa-tion thus ar was seen when nonaspirin NSAIDshad been used close to the time o conception,suggesting bias that could be partly explained bywomen using the drug to alleviate cramping, aprecursor to spontaneous abortion.
4
No one hasdocumented the risk o spontaneous abortionaccording to type and dosage o nonaspirinNSAIDs — both important elements to considerwhen determining causality.We perormed a nested case–control study toquantiy the risk o spontaneous abortion associ-ated with specic types and dosages o non-aspirin NSAIDs in a cohort o pregnant women,adjusting or potential conounders.
Methods
Study design
We used a nested case–control study design. Wechose this design because it shows similar eectsizes to a prospective cohort approach with time-varying exposure to medication, but with greatercomputational eciency.
6
Data collection
We used data rom the Quebec Pregnancy Reg-istry, an ongoing registry o all pregnancies inQuebec since 1997. Records in the registry are
Use o nonaspirin nonsteroidal anti-infammatory drugsduring pregnancy and the risk o spontaneous abortion
Hamid Reza Nakhai-Pour MD PhD, Perrine Broy BSc, Odile Sheehy MSc, Anick Bérard PhD
Competing interests:
Nonedeclared.This article has been peerreviewed.
Correspondence to:
Dr. Anick Bérard,anick.berard@umontreal.ca
CMAJ 
2011. DOI:10.1503 /cmaj.110454
Research
CMAJ
Background:
The association between the useo nonaspirin nonsteroidal anti-infammatorydrugs (NSAIDs) during pregnancy and the risko spontaneous abortion remains unclearbecause o inconsistent research results andthe lack o evidence or an eect due to spe-cic types or dosages o nonaspirin NSAIDs.We aimed to quantiy the associationbetween having a spontaneous abortion andtypes and dosages o nonaspirin NSAIDs in acohort o pregnant women.
Methods:
Using a nested case–control design,we obtained data rom the Quebec Preg-nancy Registry or 4705 women who had aspontaneous abortion. For each instance, werandomly selected 10 controls rom theremaining women in the registry who werematched by index date (date o the sponta-neous abortion) and gestational age. Use ononaspirin NSAIDs (identied by lled pre-scriptions) and nonuse were compared. Wealso looked or associations between dier-ent types and dosages o nonaspirin NSAIDsand having a spontaneous abortion.Analyseso associations and adjustment or conound-ing were done using conditional logisticregression.
Results:
We identied4705 cases o sponta-neous abortion (352 exposed [7.5%]); 47 050controls (1213 exposed [2.6%]). Adjusting orpotential conounders, the use o nonaspirinNSAIDs during pregnancy was signicantlyassociated with the risk o spontaneous abor-tion (odds ratio [OR] 2.43, 95% condenceinterval [CI] 2.12–2.79). Specically, use odicloenac (OR 3.09, 95% CI 1.96–4.87),naproxen (OR 2.64, 95% CI 2.13–3.28), celecoxib(OR 2.21, 95% CI 1.42–3.45), ibuproen (OR2.19, 95% CI 1.61–2.96) and roecoxib (OR 1.83,95% CI 1.24–2.70) alone, and combinationsthereo (OR 2.64, 95% CI 1.59–4.39), were allassociated with increased risk o spontaneousabortion. No dose–response eect was seen.
Interpretation:
Gestational exposure to anytype or dosage o nonaspirin NSAIDs mayincrease the risk o spontaneous abortion.These drugs should be used with caution dur-ing pregnancy
 Abstract
© 2011 Canadian Medical Association or its licensors
CMAJ
1
 
Early release, published at www.cmaj.ca on September 6, 2011. Subject to revision.
 
linked to those in three administrative databases:the Régie de l’assurance maladie du Québec(RAMQ) database, Med-Écho and the Institut dela statistique du Québec.The RAMQ database contains prospectivelycollected inormation on medical services, lledprescriptions, physician-based diagnoses (ac-cording to the
 International Classifcation o 
Research
2
CMAJ
Table 1:
Characteristics of cases and controlsNo. (%)*CharacteristicCases(
n = 4 705
)Controls(
n = 47 050
)
 p
value†Age on gestation day 1, yr, mean (SD) 28.7 (6.6) 27.4 (5.6) < 0.0001Gestational age at index date, w, mean (SD) 10.5 (4.2) 10.5 (5.6) 0.99Urban residence 3 676 (78.1) 36 208 (77.0) 0.07Receiving social assistance 1 618 (34.4) 14 044 (29.8) < 0.0001Use of medication from start of pregnancy to index dateUse of NSAIDs 352 (7.5) 1 213 (2.6) < 0.0001Use of other medications 1.00Antidepressant agents 227 (4.8) 1 159 (2.5) < 0.0001Systemic anti-infective agents 721 (15.3) 6 544 (13.9) 0.008Oral corticosteroids 60 (1.3) 283 (0.6) < 0.0001Antiemetic agents 162 (3.4) 7 151 (15.2) < 0.0001Other 1 937 (41.2) 13 544 (28.8) < 0.0001Prenatal visits, no.0–2 4 231 (89.9) 28 587 (60.8) 1.00
3474 (10.1) 18 463 (39.2) < 0.001Comorbidities during year before pregnancyDiabetes mellitus 77 (1.6) 459 (1.0) < 0.0001Cardiovascular disease 81 (1.7) 667 (1.4) 0.10Asthma 932 (19.8) 8 099 (17.2) < 0.0001Untreated thyroid disease 23 (0.5) 165 (0.4) 0.13Depression and/or anxiety 314 (6.7) 2 080 (4.4) < 0.0001Systemic lupus erthematosus 1 (0.0) 5 (0.0) 0.52Rheumatoid arthritis 9 (0.2) 64 (0.1) 0.34Visits to a physician during year before pregnancy, no.0–2 1 298 (27.6) 15 248 (32.4) 1.003–5 1 105 (23.5) 11 594 (24.6) 1.00
62 302 (48.9) 20 208 (43.0) < 0.0001Different prescribers, no.
 
0–2 3 286 (69.8) 34 697 (73.7) 1.00
31 419 (30.2) 12 353 (26.3) < 0.0001Visited emergency department or admitted to hospital duringyear before pregnancy727 (15.4) 6 807 (14.5) 0.07Obstetric complicationsHistory of spontaneous abortion 73 (1.6) 706 (1.5) 0.78History of planned abortion 179 (3.8) 1 441 (3.1) 0.005Use of medications during year before pregnancyNonaspirin NSAIDs 833 (17.7) 7 028 (14.9) < 0.0001Antidepressant agents 364 (7.7) 2 469 (5.2) < 0.0001Systemic anti-infective agents 1 878 (39.9) 17 184 (36.5) < 0.0001Systemic corticosteroids 108 (2.3) 982 (2.1) 0.34Other 3 217 (68.4) 30 452 (64.7) < 0.0001
Note: NSAID = nonsteroidal anti-inflammatory drug, SD = standard deviation.*Unless otherwise indicated.†Pearson
χ
2
test.
 
 
 Diseases, 9th revision
), visits to physicians andemergency departments, medical procedures,admissions to hospital, characteristics o patientsand providers o health care. The RAMQ coversthe health care costs o all residents o Quebec,but it only covers a portion o the cost o medica-tions. People covered by the drug portion o theplan include those aged 65 years and older,recipients o social assistance and workers andtheir amilies who do not have access to a privatedrug insurance program. These people accountor about 43% o the overall population o Que-bec and 36% o pregnant women in theprovince.
7
Med-Écho is a provincial database thatrecords data on admissions to acute care hospi-tals or all residents o Quebec. These datainclude the gestational ages (dened rom therst day o the last menstrual period to the end o pregnancy, as conrmed by ultrasound) orplanned and clinically detected spontaneousabortions and deliveries.The Institut de la statistique du Québec data-base provides data on all births and deaths in Que-bec, including birth weight and gestational age.Women are ollowed in the Quebec Preg-nancy Registry rom the date o entry (the rstday o the last menstrual period, as conrmed byultrasound) until the end o pregnancy. Datarecorded in these three databases have been vali-dated previously.
8–10
Studies involving pregnantwomen insured by the RAMQ or their medica-tions have been shown to generate valid risk esti-mates.
7
Our study was approved by the Centrehospitalier universitaire Ste-Justine Ethics Com-mittee, and the linkage between databases wasapproved by the Commission d’accès à l’inor-mation du Québec.
Study population
We included all women who were 15–45 yearsold on the rst day o gestation who were contin-uously insured by the RAMQ drug plan or atleast 12months beore and during their pregnan-cies. Women who had a planned abortion, whohad spontaneous abortions ater 20 weeks’ gesta-tion or who had been exposed to misoprostol,NSAID suppositories or known teratogensbeore 20 weeks’ gestation were exluded. Foreach individual woman, only her rst pregnancymeeting our eligibility criteria was included.
Selection o cases and controls
Our case denition was a clinically detectedspontaneous abortion occurring between the starto pregnancy and 20weeks’ gestation. Indexdate was dened as the calendar date o the clini-cally detected spontaneous abortions. Because
Research
CMAJ
3
Table 2:
Association between the use and the percent maximum daily doses of different nonaspirinNSAIDs and risk of having a spontaneous abortionOR (95% CI)VariableControls
n = 47 050
Cases
n = 4 705
Crude Adjusted*Type of NSAIDNone 45 837 (97.4) 4 353 (92.5) 1.00 1.00Naproxen 435 (0.9) 133 (2.8) 3.22 (2.65–3.92) 2.64 (2.13–3.28)Ibuprofen 258 (0.6) 61 (1.3) 2.49 (1.88–3.30) 2.19 (1.61–2.96)Rofecoxib 152 (0.3) 39 (0.8) 2.70 (1.90–3.85) 1.83 (1.24–2.70)Diclofenac 82 (0.2) 31 (0.7) 3.99 (2.63–6.03) 3.09 (1.96–4.87)Celocoxib 111 (0.2) 30 (0.6) 2.85 (1.90–4.27) 2.21 (1.42–3.45)Other 57 (0.1) 32 (0.7) 2.86 (1.93–4.23) 2.65 (1.71–4.12)Combination 118 (0.2) 26 (0.6) 4.80 (3.02–7.65) 2.64 (1.59–4.39)Maximum daily dose, %None 45 837 (97.4) 4 353 (93.0) 1.00 1.001–50 228 (0.5) 59 (1.3) 2.73 (2.05–3.64) 2.61 (1.90–3.59)51–65 259 (0.6) 56 (1.2) 2.28 (1.70–3.05) 1.90 (1.39–2.61)66–80 365 (0.8) 120 (2.6) 3.47 (2.81–4.27) 2.55 (2.03–3.21)
81304 (0.6) 91 (1.9) 3.16 (2.49–4.00) 2.55 (1.96–3.32)Unknown 57 (0.1) 26 (0.6)
Note: CI = confidence interval, NSAID = nonsteroidal anti-inflammatory drug, OR = odds ratio.*Odds ratios were adjusted for confounders listed in Methods.

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