Relationship Between Rheumatoid Arthritis, Fertility, and Pregnancy
Rheumatoid arthritis (RA) is an autoimmune disease
that occurs more commonly in females than in males and frequently
occurs in females of reproductive age. However, few studies address
the impact of RA on pregnancy, as many females with RA have uneventful
pregnancies with no significant complications. Published literature
contains some contradictory data in regard to pregnancy complications,
including spontaneous abortion, preeclampsia, in utero growth retardation, and preterm delivery.
Rheumatoid Arthritis and Fertility
Although fertility is generally not impaired
in females with RA, fecundity, or the ability to reproduce, may be
reduced.4833,8139 In
a retrospective, observational study, the effect of RA on fertility
was evaluated in females with recent onset of RA.4836 The
medical records of female residents of Olmsted County in southeastern
Minnesota, acquired from the Olmsted Epidemiology Data Base, were
retrospectively reviewed. The candidate population (n=324) consisted of females who were at least 22 years of age between 1950
and 1982, were diagnosed with RA during the same time period, and
were married prior to age 40. Controls (n=325) were matched by age,
age at first marriage, and age span of Olmsted County residents.
The results indicated that, in this study, married
females with RA had a 15% lower overall fertility rate compared to
controls. In addition, females with RA experienced a longer time-to-conception
compared to controls, regardless of prior pregnancies. This was observed
for pregnancies preceding, as well as following, the onset of RA.
Significant differences were seen in first, second, and third pregnancies,
and the greatest difference in time-to-conception was observed for
the first pregnancy (P=0.0002). The prolonged time-to-conception was associated with the presence
of rheumatoid factor, an immunoglobulin M autoantibody.4836 Low fecundity of females who later develop RA may be explained,
in part, by low coital rates, which are caused by the low androgen
levels, characteristic of people who develop RA.4834
Rheumatoid Arthritis and Pregnancy
Approximately 70% of females with RA experience
some remission of symptoms during pregnancy, with symptom relief occurring
most often during the first trimester.4831 In
many cases, once symptoms improve, symptom relief persists and may
become nearly complete as the pregnancy progresses. However, the degree
of disability, duration of the disease, and a positive or negative
RF were not reliable predictors of the course of RA during the pregnancy
experience.8140 Approximately
25% of RA patients continue to have active disease or worsening of
disease during pregnancy, which may require treatment.8141
Many times, regardless of gestational disease
status, the symptoms of RA will be reactivated within 3-4 months post
partum.8141 One prospective cohort study conducted
in the Netherlands, which followed females with RA (N=84) from preconception or early pregnancy through the postpartum period,
found that the total number of patients in remission increased from
17% in the first trimester to 27% in the second trimester (P=0.16), despite marked reduction in
medications used to control RA.11903 However,
by the 12th week post partum, only 18% were reported to be in remission,
with at least 39% (33 of 84) of females having experienced either
a severe (n=3) or moderate disease flare (n=30) by 26 weeks post partum.11903 Another study examining the molecular mechanisms related
to RA remission during pregnancy and postpartum reactivation found
that clinical remission of RA during pregnancy was associated with
monocyte activation similar to that seen in healthy pregnant females
used as a control population.11904 Researchers
found that monocyte gene activity, which was elevated during pregnancy
in females with RA and matched controls, decreased after delivery
in controls, but it persisted in the RA population.11904 Further analysis of relevant cellular pathways indicated
that the interaction of monocytes with recurring lymphocyte activity
may play a key role in postpartum reactivation of RA.11904
The published literature surrounding complications
during pregnancy in females with RA remains contradictory. Some studies
suggest that females with RA are at an increased risk for spontaneous
abortion, premature delivery, and small-for-gestational-age infants.4832,4833,4841,4849,4850 However,
a number of studies have conversely suggested that the inflammatory
processes of RA are not associated with impaired fetal development
or with an increased risk of maternal complications during pregnancy.4841,4843,4844 In
fact, one report suggests the rate of spontaneous abortion to be 15%-25%
in females with RA, which compares to the rate observed in the general
population.4842 In
a 2009 publication, de Man, et al., reported findings of a prospective
study designed to evaluate the potential relationship between pregnancy
outcomes and RA activity.12544In this study,
disease activity was evaluated, when possible, before conception,
each trimester, and during the postpartum period for 152 RA patients
with singleton pregnancies. 12544 Results showed that pregnancy outcomes in females with stable
RA were comparable to the general population.12544 However, a higher level of RA activity was associated with
lower birth weight infants (P=0.025).12544
Rarely, patients with severe hip or knee involvement
may require cesarean section.4845,4847,4848 Additionally,
spine and hip disease may make epidural anesthesia and vaginal delivery
difficult.8151
Content on this page was last reviewed
on
January 01, 2010.
Content on this page was last changed on
March 19, 2009.
References:
4831.
Ostensen M. Sex hormones and pregnancy in rheumatoid arthritis and
systemic lupus erythematosus [discussion 144].
Ann N Y Acad
Sci.
1999;876:131-143.
4832.
Belilos E, Carsons S. Rheumatologic
disorders in women.
Med Clin North Am
. 1998;82(1):77-101.
4833.
Nelson JL, Ostensen M. Pregnancy
and rheumatoid arthritis.
Rheum Dis Clin North Am.
1997;23(1):195-212.
4834.
James W. Rheumatoid arthritis, fecundity, and coital rates: Comment
on the article by Nelson et al.
Arthritis Rheum.
1993;36(11):1637.
4836.
del Junco DJ.
The Relationship Between Rheumatoid Arthritis
and Reproductive Function
[dissertation]. Houston: University
of Texas; 1988.
4841.
Richardson A. Rheumatoid
arthritis and motherhood.
Nurs Times
. 1997;93(36):54-57.
Pitkin RM. Autoimmune diseases
in pregnancy.
Semin Perinatol.
1977;1(2):161-168.
4849.
Chambers CD, Johnson DL, Jones KL. Pregnancy outcomes in women exposed
to anti-TNF-alpha medications: the OTIS rheumatoid arthritis in pregnancy
study.
Arthritis Rheum.
2004;50(suppl 9):S479-S480.
4850.
Chakravarty EF, Nelson L, Krishnan E. Obstetric hospitalizations
in the United States for women with systemic lupus erythematosus and
rheumatoid arthritis.
Arthritis Rheum
. 2006;54(3):899-907.
8139.
Pope JE, Bellamy N, Stevens A. The lack of associates between rheumatoid
arthritis and both nulliparity and infertility.
Semin Arthritis
Rheum.
1999;28(5):342-250.
8140.
Stanworth DR. A possible immunochemical explanation for pregnancy
associated remissions in rheumatoid arthritis?
Ann Rheum Dis
. 1988;47(2):89-90.
8141.
Barrett JH, Brennan P, Fiddler M, Silman AJ. Does rheumatoid arthritis
remit during pregnancy and relapse postpartum? Results from a nationwide
study in the United Kingdom performed prospectively from late pregnancy.
Arthritis Rheum.
1999;42(6):1219-1227.
8151.
Østensen M, Fuhrer L, Mathieu R, Seitz M, Villiger PM. A prospective
study of pregnant patients with rheumatoid arthritis and ankylosing
spondylitis using validated clinical instruments.
Ann Rheum
Dis.
2004;63(10):1212-1217.
11903.
de Man YA, Dolhain RJ, van de Geijn FE, Willemsen SP, Hazes JM. Disease
activity of rheumatoid arthritis during pregnancy: results from a
nationwide prospective study.
Arthritis Rheum.
2008;59(9):1241-1248.
11904.
Häupl
T, Østensen M, Grützkau A, Radbruch A, Burmester G-R, Villiger
PM. Reactivation of rheumatoid arthritis after pregnancy.
Arthritis Rheum.
2008;58(10):2981-2992.
12544.
de Man YA, Hazes JM, van der Heide H, et al. Association of higher
rheumatoid arthritis disease activity during pregnancy with lower
birth weight: results of a national prospective study.
Arthritis
Rheum.
2009;60(11):3196-3206.
Chambers CD, Johnson DL, Jones KL. Pregnancy outcomes in women exposed
to anti-TNF-alpha medications: the OTIS rheumatoid arthritis in pregnancy
study.
Arthritis Rheum.
2004;50(suppl 9):S479-S480.
Chakravarty EF, Nelson L, Krishnan E. Obstetric hospitalizations
in the United States for women with systemic lupus erythematosus and
rheumatoid arthritis.
Arthritis Rheum
. 2006;54(3):899-907.
Pope JE, Bellamy N, Stevens A. The lack of associates between rheumatoid
arthritis and both nulliparity and infertility.
Semin Arthritis
Rheum.
1999;28(5):342-250.
Barrett JH, Brennan P, Fiddler M, Silman AJ. Does rheumatoid arthritis
remit during pregnancy and relapse postpartum? Results from a nationwide
study in the United Kingdom performed prospectively from late pregnancy.
Arthritis Rheum.
1999;42(6):1219-1227.
Østensen M, Fuhrer L, Mathieu R, Seitz M, Villiger PM. A prospective
study of pregnant patients with rheumatoid arthritis and ankylosing
spondylitis using validated clinical instruments.
Ann Rheum
Dis.
2004;63(10):1212-1217.
de Man YA, Dolhain RJ, van de Geijn FE, Willemsen SP, Hazes JM. Disease
activity of rheumatoid arthritis during pregnancy: results from a
nationwide prospective study.
Arthritis Rheum.
2008;59(9):1241-1248.
Häupl
T, Østensen M, Grützkau A, Radbruch A, Burmester G-R, Villiger
PM. Reactivation of rheumatoid arthritis after pregnancy.
Arthritis Rheum.
2008;58(10):2981-2992.
de Man YA, Hazes JM, van der Heide H, et al. Association of higher
rheumatoid arthritis disease activity during pregnancy with lower
birth weight: results of a national prospective study.
Arthritis
Rheum.
2009;60(11):3196-3206.