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c o m Obstetrics 17

D , PREGN ,
First-Trimester Screening R U G S
AND LACTAT
A N C Y
I O N

Works Well in Clinics Rheumatoid Arthritis Drugs

BY ROBERT FINN
San Francisco Bureau
Weill Medical College of Cornell Univer-
sity, New York.
T he autoimmune disorder rheuma- traindicated in pregnancy. Exposure of
toid arthritis occurs in about 1%- unplanned pregnancies will probably
2% of the population. The disease is occur because the drug and its active
At their clinic, 4,883 pregnant women, more prevalent in women than men by metabolite may take up to 2 years to
R E N O , N E V. — First-trimester aneu- who together had 5,167 fetuses, were of- about a 3:1 ratio, but in the reproduc- reach nondetectable plasma levels.
ploidy screening is practical not just in the fered first-trimester aneuploidy screening, tive years, the ratio may be as high as The folic acid antagonist methotrexate
context of clinical trials but also in the and 2,515 women agreed. 6:1. During pregnancy, the incidence is is contraindicated during pregnancy. The
everyday world of the clinic, according to Of those pregnancies, there were a to- about 1:1,000. drug is associated with spontaneous
a poster presented by Sriram C. Perni, tal of 37 aneuploid fetuses—1 with tri- RA is characterized by the production abortions and a spectrum of congenital
M.D., and colleagues at the annual meet- somy 13, 8 with trisomy 18, 22 with tri- of cytokines, including tumor necrosis defects collectively termed methotrex-
ing of the Society for Maternal-Fetal somy 21, 4 with 45X, 1 with 47XXY, and 1 factor– (TNF- ) and interleukin-1 in ate embryopathy. The critical exposure
Medicine. with triploidy. the synovial cavity, and irreversible dam- period for structural defects is 8-10 weeks
Among 2,515 women evaluated at a sin- Of the 22 cases of trisomy 21, 3 result- age to soft tissues and bones. Drug ther- after the first day of the last menstrual pe-
gle institution, trisomy 21 was detected in ed in a live birth, and 19 were electively ter- apy of RA involves the use riod. Exposure after this
91% of 22 pregnancies when the false-pos- minated. All eight fetuses with trisomy 18 of disease-modifying an- period is associated with
itive rate was set to 5% and in 77% of 22 were electively terminated. tirheumatic drugs fetal toxicity and mortality.
pregnancies when the false-positive rate Asked in an interview whether first- (DMARDs) to prevent or The critical dose is
was set to 1%. trimester aneuploidy screen- lessen this damage. The thought to be 10 mg or
In that same group, tri- ‘We can get ing remained controversial, therapy can be categorized more per week.
somy 18 was detected in Dr. Perni replied, “I don’t as biologic DMARDs, syn- Another folate antago-
all eight affected pregnan- information for think it’s controversial, but thetic DMARDs, and anti- nist, sulfasalazine, does not
cies, whether the false-pos- couples and right now it’s not the stan- inflammatory agents. appear to cause develop-
itive rate was set to 5% or dard of care. There needs to Biologic DMARDs in- mental toxicity, but sup-
1%. women be more evidence that it’s clude three agents that in- plemental folic acid (1
Aneuploidy screening in specifically very reproducible at a single in- hibit TNF- —adalimum- mg/day) should be used if
the first trimester relies on stitution like this. ab (Humira), etanercept B Y. G E R A L D G . there is a risk of un-
an algorithm incorporat-
early on to help “This is a very, very good (Enbrel), and infliximab B R I G G S, B. P H A R M .
planned pregnancy or if
ing four pieces of data: ma- them determine test,” continued Dr. Perni, (Remicade)—and one in- pregnancy occurs. The
ternal age, blood levels of terleukin-1 receptor antagonist, anakin- drug has caused bloody diarrhea in a
pregnancy-associated plas-
what they want to who disclaimed any finan-
cial interest in the test. ra (Kineret). Although the human preg- nursing infant, so breast-feeding should
ma protein A (PAPP-A), do.’ “It can be done very early nancy data for these four drugs are very be undertaken cautiously. Penicillamine,
blood levels of free  -hu- and has a very good detec- limited or completely absent, animal a chelating agent, is linked with a risk of
man chorionic gonadotrophin (free tion rate for fixed false-positive rates,” he reproduction data suggest they pose a fetal connective tissue defects (cutis laxa)
 –hCG), and ultrasound measurements said. low risk for developmental toxicity and should be avoided during pregnancy.
of fetal nuchal translucency, Dr. Perni He said that many insurance carriers in (growth retardation, structural defects, The anti-inflammatory agents in-
said. New York City do cover the screening test. functional/behavioral defects, or death). clude prednisone and the nonsteroidal
A large, multicenter, clinical trial in- And while the test has become “almost the The safest course is to avoid these anti-inflammatory drugs (NSAIDs),
volving 8,514 patients found this algo- standard of care” in certain parts of the agents during the first trimester, but which include aspirin. There is consid-
rithm to have a good sensitivity and an ac- United States, “it just hasn’t become vogue with their long elimination half-lives, in- erable potential for embryo/fetal toxi-
ceptable false-positive rate (N. Engl. J. over the whole country.” advertent exposures during organogen- city from NSAIDs: spontaneous abor-
Med. 2003;349:1405-13). He added, “I think the most exciting esis of unplanned pregnancies is likely. tions when used around the time of
But it remained unclear whether the al- thing about this is that we can get infor- The synthetic DMARDs include aza- conception, fetal renal toxicity, and pre-
gorithm would perform as well in the mation for couples and women specifically thioprine (Imuran), cyclosporine mature closure of the ductus arteriosus
real-world setting of a single institution, very early on to help them determine (Sandimmune, Neoral), gold com- in the third trimester. Aspirin use near
reported Dr. Perni and his colleagues at what they want to do.” ■ pounds, hydroxychloroquine (Plaque- term may increase the risk of bleeding
nil), leflunomide (Arava), methotrex- in the mother and the infant. The use
ate, penicillamine, and sulfasalazine of prednisone during organogenesis
Large Study Confirms Benefit of (Azulfidine). carries a low risk for oral clefts and pro-
The immunosuppressants, azathio- longed use in pregnancy has been as-
prine and cyclosporine, do not appear to sociated with growth retardation.
Oral Tocolysis Maintenance cause congenital defects, but may be as- The biologic DMARDs, gold com-
sociated with growth retardation. There pounds, hydroxychloroquine, NSAIDs
R E N O , N E V. — While many physi- were included in the study. Women with is limited human pregnancy experience (except high-dose aspirin), and pred-
cians commonly use oral tocolysis main- premature rupture of membranes and with the gold compounds—auranofin nisone are likely compatible with breast-
tenance after intravenous tocolysis in pa- medically indicated inductions before 37 (Ridaura), aurothioglucose (Solganal), feeding. The other agents are con-
tients with preterm labor because they weeks of gestation were excluded from and gold sodium thiomalate (Auro- traindicated (methotrexate) or should
have a clinical impression of its effective- the analysis. late)—but the animal data suggest the be avoided due to potential toxicity.
ness, solid evidence for this practice has Investigators compared 4,936 women risk for developmental toxicity is low. The Organization of Teratology In-
been lacking until recently, according to who received oral maintenance tocolysis Hydroxychloroquine is probably formation Services is conducting a
Perkin Stang, M.D., of Wayne State Uni- with a  –sympathomimetic agent to 4,536 compatible in pregnancy. However, study of pregnancy exposure to
versity, Detroit, and colleagues. women who did not receive oral tocolysis. there is limited pregnancy experience rheumatoid arthritis drugs. Health care
Their population-based historical co- (Data were unavailable for the remaining with the high doses commonly used in professionals may call toll-free (877-
hort study suggests that pregnant patients 70 patients.) RA. The drug has a very long elimina- 311-8972) for information on enrolling
who are not maintained on oral tocolysis In the oral tocolysis group, 366 patients tion half-life from maternal tissues patients in this study.
are more than twice as likely to deliver (7%) delivered prematurely versus 1,094 (weeks to months). Thus, stopping the
prematurely as are those who do receive patients (24%) in the control group. drug when pregnancy is confirmed will MR. BRIGGS is pharmacist clinical
oral maintenance, the investigators re- After adjusting the results for possible not prevent embryo/fetal exposure. specialist, Women’s Pavilion at Miller
ported in a poster presentation at the an- confounding variables such as prior Leflunomide, a pyrimidine synthesis Children’s Hospital, Long Beach, Calif.;
nual meeting of the Society for Maternal- preterm delivery, cerclage, incompetent inhibitor, causes dose-related terato- clinical professor of pharmacy, University
Fetal Medicine. cervix, duration of intravenous tocolysis, genicity and toxicity in animals at dos- of California, San Francisco; and
The study involved 170,258 patients and obesity, investigators calculated an es much lower than those used in hu- adjunct professor, University of Southern
from a perinatal database in the state of odds ratio of 2.4 for preterm delivery in mans. Human pregnancy experience is California, Los Angeles. He also is
Schleswig-Holstein, Germany. patients who were not maintained on too limited to determine the risk to the coauthor of “Drugs in Pregnancy and
Of those patients, 9,542 with preterm la- oral tocolysis. embryo or fetus, and the drug is con- Lactation.”
bor who received intravenous tocolysis —Robert Finn