Systematic Review: Is the Use of NSAIDs Safe During Pregnancy in Women With Rheumatic Disease?

Martínez López, Juan Antonio

doi:10.1016/S2173-5743(08)70186-2

Article information

Abstract

Bibliography

Download PDF

Statistics

Objective

To analyze the security of non-steroidal anti-inflammatory drugs (NSAID) in rheumatic disease patients during pregnancy.

Methods

We performed a systematic review using a sensitive search strategy. All studies published in MEDLINE (since 1961), EMBASE (since 1961), and Cochrane Library (up to January 2008) were selected. We defined the population (pregnant women 16 years or above with a musculoskeletal disease), the intervention (use of NSAID), and the outcomes related to safety (number of live births, stillbirths, length of gestation and of labour, birth-weight, number and type of congenital malformations). The titles and abstracts of articles retrieved from the search were reviewed and high quality cohorts and case-control studies were included.

Results

Of a total of 149 references retrieved, only 8 were analyzed in detail, and 3 were finally included. More than 2600 pregnant patients were analyzed. There are many different NSAIDs as well as many different outcomes. Different NSAID were included as well as different outcomes. There was no increased risk of congenital malformations in 2 of the studies. In the third one there was an increased risk for cardiac malformations (OR=1.86; 95% CI, 1.32-2.62) and orofacial clefts (OR=2.61; 95% CI, 1.01-6.78).

Conclusions

There is not enough information to support the negative effects of NSAIDs during pregnancy. On the other hand there is one study suggesting that the use of NSAIDs could increase the risk of cardiac and orofacial malformations in newborns, therefore these drugs should be used with caution.

Key words:

Non-steroidal anti-inflammatory drugs

Pregnancy

Congenital malformation

Objetivo

Analizar la seguridad del tratamiento con antiinflamatorios no esteroideos (AINE) en embarazadas con afección reumática.

Métodos

Revisión sistemática. Se definió una estrategia de búsqueda bibliográfica sensible en MEDLINE (desde 1961), EMBASE (desde 1980) y Cochrane Library (hasta enero de 2008); se definió la población (mujeres embarazadas mayores de 16 años con enfermedad reumática) y la intervención (tratamiento con AINE); se midió, como resultados, el número de recién nacidos vivos, las pérdidas fetales, la duración de la gestación y del parto, el peso del recién nacido y número y tipo de malformaciones congénitas. Se revisaron, por título y resumen, los artículos recuperados de la búsqueda y se incluyeron estudios de cohortes y de casos y controles.

Resultados

De un total de 149 artículos rescatados, se seleccionaron 8 para lectura en detalle, de los que finalmente se seleccionaron 3, que incluyeron a más de 2.600 pacientes embarazadas. Destaca la gran variedad en el tipo de AINE y en las medidas de desenlace. En 2 de los artículos no se encontró un aumento del riesgo de malformaciones, mientras que en el tercero se observó un aumento del riesgo de malformaciones cardíacas (odds ratio [OR] = 1,86; intervalo de confianza [IC] del 95%, 1,32-2,62) y orofaciales (OR = 2,61; IC del 95%, 1,01–6,78).

Conclusiones

No hay suficientes datos de que no sea seguro el uso de AINE durante el embarazo. Por otro lado, un estudio apunta que la utilización de AINE podría relacionarse con un discreto aumento en la frecuencia de malformaciones cardíacas y orofaciales, por lo que es aconsejable usar estos fármacos con precaución en el embarazo.

Palabras clave:

Antiinflamatorios no esteroideos

Embarazo

Malformación congénita

Full text is only aviable in PDF

References

[1.]

P.M. Brooks, C.J. Needs.

Antirheumatic drugs in pregnancy and lactation.

Bailliere's Clinical Rheumatology, 4 (1990), pp. 157-171

Medline

[2.]

G.G. Briggs, R.K. Freeman, S.J. Yaffe.

Drugs in pregnancy and lactation.

6.a, Lippincott Williams and Wilkins, (2002),

[3.]

S.T. Vermillion, J.A. Scardo, A.G. Lashus, H.B. Wiles.

The effect of indomet hacin toxolysis on fetal ductus arteriosus constriction with advancing ges tational age.

Am J Obstet Gynecol, 177 (1997), pp. 256-259

Medline

[4.]

K.K. Temprano, R. Bandlamudi, T.L. Moore.

Antirheumatic drugs in pregnancy and lactation.

Semin Arthritis Rheum, 35 (2005), pp. 112-121

http://dx.doi.org/10.1016/j.semarthrit.2005.05.002 | Medline

[5.]

M. Østensen, M. Motta.

Therapy insight: The use of antirheumatic drugs during nursing.

Nat Clin Pract Rheumatol, 3 (2007), pp. 400-406

http://dx.doi.org/10.1038/ncprheum0532 | Medline

[6.]

Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001) [cited Apr 14, 2008]. Available at: http://www.cebm.net/in-dex.aspx?o=1025

[7.]

R.B. Lewis, J.D. Schulman.

Influence of acetylsalicylic acid, an inhibitor of prostaglandin synthesis, on the duration of human gestation and labour.

Lancet, 2 (1973), pp. 1159-1161

Medline

[8.]

M. Østensen, H. Østensen.

Safety of nonsteroidal anti-inflammatory drugs in pregnant patients with rheumatic disease.

J Rheumatol, 23 (1996), pp. 1045-1049

Medline

[9.]

A. Ericson, B.A. Kallen.

Nonsteroidal anti-inflammatory drugs in early pregnancy.

Reprod Toxicol, 15 (2001), pp. 371-375

Medline

[10.]

J. Warkany, E. Takacs.

Experimental production of congenital malformations in rats by salicylate poisoning.

Am J Pathol, 35 (1959), pp. 315

Medline

[11.]

D.G. Transler.

Aspirin-induced cleft lip and other malformations in mice.

Lancet, 1 (1965), pp. 606

Medline

[12.]

A.K. Palmer.

Sporadic malformation in laboratory animals.

Adv Exp Med Biol, 27 (1972), pp. 48

[13.]

M. Østensen, R. Ramsay-Goldman.

Treatments of inflammatory rheumatic disorders in pregnancy.

Drug Safety, 19 (1998), pp. 389-410

Medline

[14.]

P.M. Brooks, C.J. Needs.

The use of antirheumatic medication during pregnancy and in the puerperium.

Rheum Dis Clin North Am, 15 (1989), pp. 789-806

Medline

[15.]

E. Kozer, S. Nikfar, A. Costei, R. Boskovic, I. Nulman, G. Koren.

Aspirin consumption during the first trimester of pregnancy and congenital anomalies: a meta-analysis.

Am J Obstet Gynecol, 187 (2002), pp. 1623-1630

Medline

[16.]

D.K. Li, L. Liu, R. Odouli.

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study.

BMJ, 327 (2003), pp. 368

http://dx.doi.org/10.1136/bmj.327.7411.368 | Medline

[17.]

G.L. Nielsen, H.T. Sorensen, H. Larsen, L. Pedersen.

Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study.

BMJ, 322 (2001), pp. 266-270

Medline

[18.]

J.F. Correy, N.M. Newman, J.A. Collins, E.A. Burrows, R.F. Burrows, J.T. Curran.

Use of prescription drugs in the first trimester and congenital malformations.

Aust N Z J Obstet Gynaecol, 31 (1991), pp. 340

Medline

[19.]

J.C. Pons, L. Nekhlyudov, J.F. Delfraissy.

The course of the SAPHO síndrome during pregnancy.

Eur J Obstet Gynecol Reprod Biol, 70 (1996), pp. 215-216

Medline