Effects of ibuprofen, diclofenac, naproxen, and piroxicam on ... - Sigo
Effects of ibuprofen, diclofenac, naproxen, and piroxicam on ... - Sigo
Effects of ibuprofen, diclofenac, naproxen, and piroxicam on ... - Sigo
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
Safety <str<strong>on</strong>g>of</str<strong>on</strong>g> individual NSAIDs during pregnancy<br />
Table 4. Adjusted odds ratios (ORs) for c<strong>on</strong>genital malformati<strong>on</strong>s detected at birth in children <str<strong>on</strong>g>of</str<strong>on</strong>g> women who used ibupr<str<strong>on</strong>g>of</str<strong>on</strong>g>en, dicl<str<strong>on</strong>g>of</str<strong>on</strong>g>enac,<br />
<str<strong>on</strong>g>naproxen</str<strong>on</strong>g>, or <str<strong>on</strong>g>piroxicam</str<strong>on</strong>g> during pregnancy, compared with the unexposed c<strong>on</strong>trol group<br />
Any c<strong>on</strong>genital malformati<strong>on</strong>*<br />
Use during pregnancy (total)<br />
Use during the first trimester<br />
n % OR 95% CI n % OR 95% CI<br />
Women who did not use any 4010/83 906 4.8 ref. ref. 4010/83 906 4.8 ref. ref.<br />
NSAIDs during pregnancy<br />
Ibupr<str<strong>on</strong>g>of</str<strong>on</strong>g>en 247/5325 4.6 1.0 0.8–1.1 140/3034 4.6 1.0 0.8–1.1<br />
Dicl<str<strong>on</strong>g>of</str<strong>on</strong>g>enac 17/491 3.5 0.7 0.4–1.2 5/192 2.6 0.5 0.2–1.3<br />
Naproxen 14/354 4.0 0.8 0.5–1.4 9/168 5.4 1.1 0.6–2.2<br />
Piroxicam 6/150 4.0 0.8 0.4–1.9 4/82 4.9 1.0 0.4–2.8<br />
Major c<strong>on</strong>genital malformati<strong>on</strong>*<br />
Women who did not use any 2203/83 906 2.6 ref. ref. 2203/83 906 2.6 ref. ref.<br />
NSAIDs during pregnancy<br />
Ibupr<str<strong>on</strong>g>of</str<strong>on</strong>g>en 130/5325 2.4 0.9 0.8–1.1 73/3034 2.4 0.9 0.7–1.2<br />
Dicl<str<strong>on</strong>g>of</str<strong>on</strong>g>enac 12/491 2.4 0.9 0.5–1.6 2/192 1.0 0.4 0.1–1.5<br />
Naproxen 9/354 2.5 1.0 0.5–1.9 7/168 4.2 1.6 0.7–3.5<br />
Piroxicam 3/150 2.0 0.7 0.2–2.3 2/82 2.4 0.9 0.2–3.8<br />
Structural heart defect detected during the first 18 m<strong>on</strong>ths <str<strong>on</strong>g>of</str<strong>on</strong>g> age**<br />
Women who did not use any 1001/83 906 1.2 ref. ref. 1001/83 906 1.2 ref. ref.<br />
NSAIDs during pregnancy<br />
Ibupr<str<strong>on</strong>g>of</str<strong>on</strong>g>en 65/5325 1.2 1.0 0.8–1.3 44/3034 1.5 1.2 1.0–1.6<br />
Dicl<str<strong>on</strong>g>of</str<strong>on</strong>g>enac 9/491 1.8 1.4 0.7–2.8 2/192 1.0 0.8 0.2–3.5<br />
Naproxen 2/354 0.6 0.9 0.5–1.9 1/168 0.6 – –<br />
Piroxicam 4/150 2.7 2.3 0.8–6.2 2/82 2.4 2.3 0.5–9.3<br />
*Data registered in the Medical Birth Registry <str<strong>on</strong>g>of</str<strong>on</strong>g> Norway.<br />
**Data self-reported by mother. Only infants referred to a specialist were included.<br />
estimates towards 1.0. On the other h<str<strong>on</strong>g>and</str<strong>on</strong>g>, some misclassificati<strong>on</strong><br />
in the opposite directi<strong>on</strong> may also have occurred<br />
because <str<strong>on</strong>g>of</str<strong>on</strong>g> the way multiple medicati<strong>on</strong>s were coded when<br />
used in multiple time periods. We could not assess dosage<br />
<str<strong>on</strong>g>and</str<strong>on</strong>g> durati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> NSAID use in detail: data that would have<br />
given us informati<strong>on</strong> about possible dose–resp<strong>on</strong>se effects.<br />
The higher frequency <str<strong>on</strong>g>of</str<strong>on</strong>g> c<strong>on</strong>comitant medicati<strong>on</strong> am<strong>on</strong>g<br />
NSAID users also merits attenti<strong>on</strong>; however, co-medicati<strong>on</strong><br />
with potential teratogens <str<strong>on</strong>g>and</str<strong>on</strong>g> other medicati<strong>on</strong>s with possible<br />
effects <strong>on</strong> certain pregnancy outcomes, <str<strong>on</strong>g>and</str<strong>on</strong>g> comm<strong>on</strong>ly<br />
used by the women, have been c<strong>on</strong>trolled for in the analyses.<br />
Despite the large sample size, we lacked power in this<br />
study to detect a possible increase in specific c<strong>on</strong>genital<br />
anomalies (<str<strong>on</strong>g>and</str<strong>on</strong>g> rare pregnancy outcomes). Finally, because<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> the large number <str<strong>on</strong>g>of</str<strong>on</strong>g> analyses performed we cannot<br />
exclude the possibility that the associati<strong>on</strong>s we did find<br />
were caused by mass significance, although some <str<strong>on</strong>g>of</str<strong>on</strong>g> these<br />
associati<strong>on</strong>s were significant at the 1% level. Our results<br />
must be interpreted with these limitati<strong>on</strong>s in mind.<br />
On the other h<str<strong>on</strong>g>and</str<strong>on</strong>g>, the fact that our study included such<br />
a large number <str<strong>on</strong>g>of</str<strong>on</strong>g> participants made it possible to analyse<br />
the effect <str<strong>on</strong>g>of</str<strong>on</strong>g> individual NSAIDs <strong>on</strong> pregnancy outcome,<br />
instead <str<strong>on</strong>g>of</str<strong>on</strong>g> evaluating the group effect <str<strong>on</strong>g>of</str<strong>on</strong>g> these drugs. Few<br />
studies have achieved this so far. We included both overthe-counter<br />
<str<strong>on</strong>g>and</str<strong>on</strong>g> prescripti<strong>on</strong> NSAID use in our study, <str<strong>on</strong>g>and</str<strong>on</strong>g><br />
the c<strong>on</strong>trol group c<strong>on</strong>sisted <str<strong>on</strong>g>of</str<strong>on</strong>g> women who did not use any<br />
NSAIDs during pregnancy. Previous studies have used data<br />
from prescripti<strong>on</strong> registries, so that <strong>on</strong>ly prescribed NSAID<br />
use could be taken into account. In additi<strong>on</strong>, in their c<strong>on</strong>trol<br />
groups, women using over-the-counter NSAIDs were<br />
not excluded. 14,15,19 In the present study, we were able to<br />
avoid these potential limitati<strong>on</strong>s. Because <str<strong>on</strong>g>of</str<strong>on</strong>g> the vast quantity<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> data in The Norwegian Mother <str<strong>on</strong>g>and</str<strong>on</strong>g> Child Cohort<br />
Study <str<strong>on</strong>g>and</str<strong>on</strong>g> the MBRN, many important c<strong>on</strong>founding factors,<br />
in particular underlying medical c<strong>on</strong>diti<strong>on</strong>s, pregnancy<br />
complicati<strong>on</strong>s, <str<strong>on</strong>g>and</str<strong>on</strong>g> lifestyle <str<strong>on</strong>g>and</str<strong>on</strong>g> medical<br />
characteristics <str<strong>on</strong>g>of</str<strong>on</strong>g> the infant were adjusted for in our study.<br />
This rigorous c<strong>on</strong>trol for c<strong>on</strong>founding factors has not been<br />
ª 2013 The Authors BJOG An Internati<strong>on</strong>al Journal <str<strong>on</strong>g>of</str<strong>on</strong>g> Obstetrics <str<strong>on</strong>g>and</str<strong>on</strong>g> Gynaecology ª 2013 RCOG 7