Until recently, small studies and limited, single-center cohorts have been the basis for decision-making related to pregnancy in rheumatoid arthritis (RA). In these studies, women with RA have been loosely associated with reduced fertility and poor pregnancy outcomes.
Inconsistent findings in past studies, however, have led a recent group of researchers to characterize in-hospital complications reported in pregnancy-related admissions for a large, nationwide sample of women with and without RA. Compared with the general obstetric population, women with RA more frequently experience complications during pregnancy such as hypertension, preterm delivery, and cesarean delivery.
Researchers of this nationwide assessment have shown that women with RA can successfully give birth when the risks are understood. The investigators suggest that heightened vigilance and careful pregnancy planning, including close antenatal and postdelivery monitoring, should be performed by a team of obstetricians and rheumatologists in order to reduce obstetric complications in women with RA.
Historically, it was thought that adverse outcomes were not associated with pregnant women. Few studies were designed to elucidate the affect of RA on events related to pregnancy. But, the affect of other rheumatic diseases on pregnancy — specifically, systemic lupus erythematosus — has long been studied. Researchers have determined a linkage to adverse obstetric outcomes in this patient population. Due to these findings, pregnancy outcomes in patients with lupus have improved drastically over the last several decades.
Although limited literature is available about the affects of RA on pregnancy, the inconsistency of findings does not lend any further support for an association between RA and adverse obstetric outcomes. However, women with RA were indeed found to be at increased risk for certain outcomes, including eclampsia, cesarean delivery, and preterm birth, and the potential to improve these outcomes has inspired the need for new larger studies comparing women with RA to the general obstetric population.
Researchers of a small number of studies on women with RA have mostly concluded that pregnancy does not reactivate or worsen RA, but several investigators have indicated that pregnant women with RA are at increased risk for maternal and fetal complications, including eclampsia, cesarean delivery, preterm birth, and infants being small for gestational age at birth. These studies were mostly single-center cohorts conducted in different countries, and different environmental factors, lifestyle, or obstetric practices potentially had an influence different pregnancy outcomes.
In addition, the introduction of disease-modifying antirheumatic drugs (DMARDS) has changed how RA is managed. RA predominantly involves women of childbearing age, so data on if and how DMARDS affect pregnancy need to be considered. Currently, the only information relating pregnancy outcomes to the use of DMARDs is mostly limited to case series.
The importance of data from a recent study published in Seminars in Arthritis and Rheumatism elevates previous findings on the effects of RA on pregnancy by utilizing the Nationwide Inpatient Sample (NIS) database, which provides data on approximately 8 million hospitalizations from 1000 hospitals yearly. The investigators queried the NIS database from 2003 to 2011, identifying all pregnancy-related and antepartum discharges for women aged 18 to 50 years; they further used diagnostic codes from the International Classification of Diseases to identify patients with RA.
Specific outcomes of interest were maternal complications (including preterm delivery, premature rupture of membranes, antepartum hemorrhage, postpartum hemorrhage, preeclampsia, eclampsia, and maternal mortality) and fetal complications of intrauterine growth retardation. Other outcomes included the number of caesarean sections performed, length of hospitalization, and associated hospitalization charges.
Between 2003 and 2011, women with a diagnosis of RA made up 0.07% of total obstetric hospitalizations: 31,439 of 42.32 million patients. The investigators determined a different demographic makeup of pregnancies that involved RA vs pregnancies without RA, namely that the mean maternal age was higher (30.5 vs 27 years; P <.001). There was a greater proportion of white women; more women were obese, reported tobacco use, and alcohol abuse; and women with RA had more comorbidities such as hypertension, diabetes, and congestive heart failure.
Compared with women who had a pregnancy without RA, women with RA experienced a higher rate of obstetric complications, longer hospital stays (3.4 vs 2.68 days), and consequently, higher hospital costs. Analysis of coded obstetric complications showed that the maternal RA population had a significantly higher prevalence of hypertensive diseases (13.5% vs 8.9%), premature rupture of membranes (5.4% vs 3.4%), antepartum hemorrhage (3% vs 2%), preterm delivery (10.2% vs 6.6%), intrauterine growth retardation (3.5% vs 1.8%), and cesarean delivery (35% vs 28%).
With these findings, the study investigators painted a complete picture of both clinical and lifestyle risks. According to researchers, the facts that the maternal age of women with RA was higher and that a higher proportion of RA pregnancies fell into the older range of maternal age groups are significant because the incidence of RA is notably higher during childbearing age. Reduced fertility is another concern among patients with RA, which could be a mechanism of hormonal dysfunction from the disease.
Because of this information, an RA diagnosis certainly impacts decisions related to childbearing, quite possibly delaying pregnancy in this patient population. Researchers indicated that clinicians should discuss the risks related to RA in pregnancy with their patients and closely monitor women with RA during pregnancy to improve outcomes.
An outcome from this large-cohort study was that, although the risk for preterm delivery was significantly higher in RA pregnancies compared with nonRA pregnancies, the prevalence of preterm births was lower. The investigators suggest that planned pregnancy may help overcome obstetric complications related to RA and lower the risk for preterm birth.
A higher prevalence of hypertensive disorders (including preeclampsia and eclampsia) was associated with RA in pregnant women, and hypertension commonly leads to complications including unplanned, high-risk cesarean delivery. Furthermore, clinicians should understand that women with RA frequently doubt their functional and physical ability to endure labor; Therefore, patients with RA might decide on an elective cesarean section.
Control of hypertensive disorders, diabetes, high disease activity, and fetal distress, along with counseling on tobacco and alcohol use, and monitoring of functional measures, may lower the risk for cesarean delivery in women with RA. This can further reduce prolonged hospitalizations and the associated hospital costs.
Although this study offers significant insight into the impact of RA on pregnancy while it highlights the value of managing RA symptoms and related risks for women of childbearing age. Investigators suggest that the relationship of pregnancy outcomes with RA severity, medication use, and comorbidities should be the subject of future studies.
1. Kishorea S, Mittalb V, Majithia V. Obstetrics outcomes in women with rheumatoid arthritis: results from nationwide inpatient sample database 2003-2011. Semin Arthritis Rheum. 2019;49:236-240.